Ferroptosis Target Information

General Information of the Ferroptosis Target (ID: TAR10055)

Target Name	Cystine/glutamate transporter (SLC7A11)
Synonyms	Amino acid transport system xc-; Calcium channel blocker resistance protein CCBR1; Solute carrier family 7 member 11; xCT Click to Show/Hide
Gene Name	SLC7A11
Sequence	MVRKPVVSTISKGGYLQGNVNGRLPSLGNKEPPGQEKVQLKRKVTLLRGVSIIIGTIIGA GIFISPKGVLQNTGSVGMSLTIWTVCGVLSLFGALSYAELGTTIKKSGGHYTYILEVFGP LPAFVRVWVELLIIRPAATAVISLAFGRYILEPFFIQCEIPELAIKLITAVGITVVMVLN SMSVSWSARIQIFLTFCKLTAILIIIVPGVMQLIKGQTQNFKDAFSGRDSSITRLPLAFY YGMYAYAGWFYLNFVTEEVENPEKTIPLAICISMAIVTIGYVLTNVAYFTTINAEELLLS NAVAVTFSERLLGNFSLAVPIFVALSCFGSMNGGVFAVSRLFYVASREGHLPEILSMIHV RKHTPLPAVIVLHPLTMIMLFSGDLDSLLNFLSFARWLFIGLAVAGLIYLRYKCPDMHRP FKVPLFIPALFSFTCLFMVALSLYSDPFSTGIGFVITLTGVPAYYLFIIWDKKPRWFRIM SEKITRTLQIILEVVPEEDKL Click to Show/Hide
Family	L-type amino acid transporter family
Function	Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane. Provides L-cystine for the maintenance of the redox balance between extracellular L- cystine and L-cysteine and for the maintenance of the intracellular levels of glutathione that is essential for cells protection from oxidative stress. The transport is sodium-independent, electroneutral with a stoichiometry of 1:1, and is drove by the high intracellular concentration of L-glutamate and the intracellular reduction of L-cystine . In addition, mediates the import of L-kynurenine leading to anti-ferroptotic signaling propagation required to maintain L-cystine and glutathione homeostasis. Moreover, mediates N-acetyl-L-cysteine uptake into the placenta leading to subsequently down-regulation of pathways associated with oxidative stress, inflammation and apoptosis. In vitro can also transport L-aspartate. May participate in astrocyte and meningeal cell proliferation during development and can provide neuroprotection by promoting glutathione synthesis and delivery from non-neuronal cells such as astrocytes and meningeal cells to immature neurons. Controls the production of pheomelanin pigment directly. Click to Show/Hide
Gene ID	23657
Uniprot ID	Q9UPY5
Target Type	Driver Suppressor Marker
Mechanism Diagram	Click to View the Original Diagram

Tissue Relative Abundances of This Target

Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)

SLC7A11 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.

Browse Regulator related Disease

Browse Regulator related Drug

Ubiquitin-fold modifier 1 (UFM1)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[1]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Metformin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	HCC1937 cells	Breast ductal carcinoma	Homo sapiens	CVCL_0290
	Bcap37 cells	Breast carcinoma	Homo sapiens	CVCL_0164
	HBL-100 cells	Normal	Homo sapiens	CVCL_4362
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	BT-549 cells	Invasive breast carcinoma	Homo sapiens	CVCL_1092
In Vivo Model	T47D xenografts were established in 5-week-old nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 10⁷ cells mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) into the abdominal mammary fat pad. When the tumor reached 50-100 mm³, the mice were assigned randomly into different treatment groups (DMSO, Metformin, SAS, and Metformin + SAS groups). Metformin (200 mg/kg/day) was provided in drinking water. Sulfasalazine was dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 250 mg/kg once a day. Click to Show/Hide
Response Description	Metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc-inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells.

Ubiquitin thioesterase OTUB1 (OTUB1)

Regulator Info

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[2]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Solasonine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	CFPAC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_1119
In Vivo Model	For xenograft assays, we subcutaneously injected 1 x 10⁶ PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment. Click to Show/Hide
Response Description	Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[36]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	BT-474 cells	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	SK-BR-3 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0033
In Vivo Model	A total of 24 NOD/SCID mice were purchased from Model Animal Research Center and grown under specific-pathogen-free condition. Mice were randomly divided into three groups (n = 8 per group), BT474-Tr cells were inoculated orthotopically onto the abdominal mammary fat pad. After 1 week, mice were treated with erastin (15 mg/kg intraperitoneal, twice every other day). Erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma). To better dissolve erastin, we warmed the tube at 37 water bath and shook it gently. At the end of the sixth week, all mice were sacrificed, tumor tissues were collected and weighed. Click to Show/Hide
Response Description	Knockdown of circ-BGN inhibited breast cancer cell viability and notably restored its sensitivity to trastuzumab. Further, we found that circ-BGN could directly bind to OTUB1 and SLC7A11, enhancing OTUB1-mediated SLC7A11 deubiquitination and thereby inhibiting ferroptosis.

Injury of intra-abdominal organs [ICD-11: NB91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[37]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
	Ubiquitin mediated proteolysis	hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	mPHs (Mouse primary hepatocytes)
In Vivo Model	ALI induction was performed in 6-8-week-old age-matched C57BL/6J male mice (n = 10-12 per group) by intraperitoneal injection of 3 mL/kg CCl4 in coconut oil. Control and negative control mice were injected with PBS and coconut oil, respectively. At 6 h after injection of CCl4, mice were divided into three groups: CCl4 group, injected with 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; CCl4 + MSC group, injected with 5 x 10⁵ MSCs suspended in 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; CCl4 + Fer-1 group, intraperitoneally injected with ferrostatin-1 (Fer-1, a ferroptosis inhibitor, 2.5 umol/kg body weight). Erastin, intraperitoneal injection of erastin (a ferroptosis inducer, 30 mg/kg body weight) twice every other day, and then the mice were divided into two groups (n = 10-12 per group): Erastin group, injected with 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; Erastin + MSC group, injected with 5 x 10⁵ MSCs suspended in 100 uL PBS (supplemented with 2% mouse serum) through the tail vein. Click to Show/Hide
Response Description	MSC-Exo protected against CCl4-induced acute liver injury (ALI) through inhibiting hepatocyte ferroptosis via restoring the SLC7A11 protein level. Additionally, the exosome-induced recovery of SLC7A11 protein was accompanied by upregulations of CD44 and OTUB1.

Health [ICD-11: N.A.]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[145]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	HEK293 cells	Normal	Homo sapiens	CVCL_0045
	SK-N-BE(2)-C cells	Neuroblastoma	Homo sapiens	CVCL_0529
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SK-RC-42 cells	Renal cell carcinoma	Homo sapiens	CVCL_6192
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	T24 cells	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3 cells	Bladder carcinoma	Homo sapiens	CVCL_1783
	SW780 cells	Bladder carcinoma	Homo sapiens	CVCL_1728
In Vivo Model	5.0 x 10⁶ cells were mixed with Matrigel (BD Biosciences) at 1:1 ratio (v/v) and injected subcutaneously into seven-week old nude mice (NU/NU; Charles River). Mice were fed with regular chow. After nine weeks, the mice were killed and the tumors were weighed and recorded. Click to Show/Hide
Response Description	Overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner.

Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[3]
Regulator for Ferroptosis	Driver
Responsed Drug	Erastin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 10⁶ cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. Click to Show/Hide
Response Description	SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[3]
Regulator for Ferroptosis	Driver
Responsed Drug	Cisplatin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 10⁶ cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. Click to Show/Hide
Response Description	SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy.

Transcription factor AP-2-alpha (TFAP2A)

Regulator Info

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[2]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Solasonine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	CFPAC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_1119
In Vivo Model	For xenograft assays, we subcutaneously injected 1 x 10⁶ PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment. Click to Show/Hide
Response Description	Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis.

Signal transducer and activator of transcription 3 (STAT3)

Regulator Info

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[4]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Bavachin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MG-63 cells	Osteosarcoma	Homo sapiens	CVCL_0426
In Vitro Model	HOS cells	Osteosarcoma	Homo sapiens	CVCL_0312
Response Description	Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression.

Head neck squamous cell carcinoma [ICD-11: 2D60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[51]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ferroptosis			hsa04216
	JAK-STAT signaling pathway			hsa04630
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HN4 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_IS30
	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
In Vivo Model	Four-week-old male BALB/c-nu mice were purchased from the Shanghai Laboratory Animal Center (Shanghai, China). About 4 x 10⁶ CAL27 cells were stably transfected with lentivirus. After administration of 2 ug/mL puromycin for three days, transfection efficiency was confirmed by western blotting. Approximately 2 x 10⁶ transfected cells were subcutaneously injected into flanks. For the drug-administration study, 20 mg/kg erastin (S7242, Selleck Chemicals) were administrated intraperitoneally twice every other day. Approximately 20 uL IL-6 (10 ug/mL, PeproTech, USA) were given intratumorally twice every other day. Click to Show/Hide
Response Description	The study demonstrate the critical role of IL-6-induced ferroptosis resistance during head and neck squamous cell carcinoma carcinogenesis. The IL-6/ STAT3/xCT (encoded by SLC7A11) axis acts as a novel mechanism driving tumor progression and thus may potentially be utilized as a target for tumor prevention and therapy.

rno-miR-23a-3p (miRNA)

Regulator Info

Supraventricular tachycardia [ICD-11: BC81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[5]
Regulator for Ferroptosis	Driver
Responsed Drug	GW4869		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
	rCFs (Rat cardiac fibroblasts)
In Vivo Model	Eighteen beagles, randomly divided into three groups, both sexes and an average age of 1 year, weighing 7.5 ± 1.5 kg, were used for the study as follows: Sham group (n = 6), Pacing group (n = 6), and GW4869 + Pacing group (n = 6). Each beagle canine was given an intramuscular injection of 25 mg/kg ketamine sulfate before being premedicated with pentobarbital sodium (30 mg/kg, intravenous injection) and ventilated with room air by a respirator (MAO01746, Harvard Apparatus Holliston, United States). Venous access was established to supply saline (50-100 mL/h) or pentobarbital sodium (2.5 mg/kg/h). Click to Show/Hide
Response Description	The exosome inhibitor GW4869 reduced ferroptosis, fibrosis, and inflammation and improved histological and electrophysiological remodeling. Pacing-CF-exos highly expressed miR-23a-3p by informatics analysis and experimental verification. Inhibitor- miR-23a-3p protected h9c2 cells from ferroptosis accompanying with upregulation of SLC7A11. The development of atrial fibrillation (AF) in a persistent direction could be prevented by intervening with exosomal miRNAs to reduce oxidative stress injury and ferroptosis.

RNA-binding motif, single-stranded-interacting protein 1 (RBMS1)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[6]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Nortriptyline hydrochloride		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Doxorubicin (Dox)- inducible RBMS1 knockdown stable cells (3 x 10⁶ ) were injected subcutaneously into the abdomen side of 6-week-old BALB/c nude mice (Vital River). Mice were fed either with sucrose water or sucrose water containing 0.1% doxycycline hyclate. H1299 vector, 4 H1299 pLKO.1 RBMS1 and H1299 pLKO.1 RBMS1/SLC7A11 cells (2.5 x 10⁶ ) were injected subcutaneously into the abdomen side of 6-week-old BALB/c nude mice(Vital River). The xenograft tumour formation was monitored using callipers every 3 days. Click to Show/Hide
Response Description	RBMS1 ablation inhibited the translation of SLC7A11, reduced SLC7A11-mediated cystine uptake, and promoted ferroptosis. Nortriptyline hydrochloride decreased the level of RBMS1, thereby promoting ferroptosis. Importantly, RBMS1 depletion or inhibition by nortriptyline hydrochloride sensitized radioresistant lung cancer cells to radiotherapy.

RAF proto-oncogene serine/threonine-protein kinase (RAF1)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[7]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Tetraarsenic tetrasulfide		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	MAPK signaling pathway			hsa04010
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	NCI-H23 cells	Lung adenocarcinoma	Homo sapiens	CVCL_1547
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	H1650-ER1 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_4V01
Response Description	On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in antiKRAS mutant lung cancer.

Protein FAM98A (FAM98A)

Regulator Info

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[8]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Metformin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	RKO cells	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	LoVo cells	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	Caco-2 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HCT 15 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	DLD-1 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC cells	Normal	Homo sapiens	CVCL_3688
In Vivo Model	A total 1 x 10⁶ SW620-vector or SW620-FAM98A cells were suspended in 100 ul PBS and injected s.c. into the back of 4- to 6-week-old male BALB/cnude mice (Laboratory Animal Unit, Southern Medical University, China). The sizes of the resulting tumors were measured weekly. Tumor volumes were calculated as follows: total tumor volume (mm³) = (Length x Width2)/2, where Length is the longest length. When the tumor sizes reached about 200 mm³, nude mice in the four groups were given PBS or 5-FU treatment (30 mg/kg, intraperitoneal injection, twice a week), respectively. Nude mice were maintained in a barrier facility in racks filtered with a high-efficiency particulate air filter. Click to Show/Hide
Response Description	The expressions of FAM98A and SLC7A11 were also downregulated after metformin treatment. And FAM98A is predominantly expressed in the colorectal cancer tissues and high FAM98A expression is usually accompanied by the high expression of SLC7A11, which usually means ferroptosis resistance.

NF-kappa-B inhibitor alpha (NFKBIA)

Regulator Info

Glioblastoma [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[9]
Regulator for Ferroptosis	Driver
Responsed Drug	RSL3		Investigative	Drug Info
Pathway Response	NF-kappa B signaling pathway			hsa04064
	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
In Vivo Model	Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 10⁶ U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm³, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks. Click to Show/Hide
Response Description	NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11.

NAD-dependent protein deacetylase sirtuin-1 (SIRT1)

Regulator Info

Status epilepticus [ICD-11: 8A66]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[10]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Quercetin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Male C57BL/6J mice (6-8 weeks of age, weighing 18-22 g) were obtained from Gempharmatech Co., Ltd (Changzhou, China). All mice were housed in cages with standard laboratory conditions: a consistent temperature of 24 , a 12 h light/dark cycle, and free access to water and food. The mice were randomized into four groups: 1) the KA group (n = 6), injected intraperitoneally with 20 mg/kg KA, as described in a previous study; while 2) the control group (n = 6), injected intraperitoneally with an equal volume of PBS; 3) the KA + QCT group (n = 6): this group was givenintragastric administrationof 50 mg/kg of QCT once daily for 21 days before KA injection based on the literature; and 4) the KA+ferrostatin1 (Fer-1) group (n = 6), injected intraperitoneally with a well-known ferroptosis inhibitor (3 mg/kg Fer-1) for 21 days before KA administration, as described in a previous study. Click to Show/Hide
Response Description	The association between the Nrf2-mediated ferroptosis pathway and seizures in a clinical setting. Quercetin effectively protects against seizure-induced neuron death in vivo and in vitro and alleviates cognitive function impairment via the SIRT1/Nrf2/SLC7A11/GPX4 pathway.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1)

Regulator Info

Ischemia/reperfusion injury [ICD-11: DB98]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[11]
Regulator for Ferroptosis	Driver
Responsed Drug	Micafungin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	The surgical procedure for establishing the myocardial I/R injury rat model was carried out as we did before. Briefly, a left thoracotomy was performed in the fourth intercostal space and the heart was exposed via opening thepericardium. The left coronary artery was surrounded with a 4-0 silk suture and a snare was formed by passing both ends of the suture via a short polyethylene tubing. Blockage of the coronary artery was conducted via clamping the snare against the heart surface. Reperfusion was performed by release of the snare. The sham group conducted the same procedure but without ischemia (the snare was not tightened). To establish the I/R injury model, the rat hearts were subjected to 1 h-ischemia plus 3 h-reperfusion. At the end, the blood and hearts were collected for assay of the creatine kinase(CK) activity and infarct size to determine the success of I/R injury model. To explore the role of MALT1 in myocardial I/R injury the underlying mechanisms, three sets of experiment were performed. Click to Show/Hide
Response Description	The inhibition of MALT1 can reduce ischemia/reperfusion-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway; and MALT1 may be used as a potential target to seek novel or existing drugs (such as micafungin) for treating myocardial infarction.

Mothers against decapentaplegic homolog 3 (SMAD3)

Regulator Info

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[12]
Regulator for Ferroptosis	Driver
Responsed Drug	Formononetin	Investigative	Drug Info
Pathway Response	Ferroptosis		hsa04216
	Fatty acid metabolism		hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mPRTECs (Mouse primary renal tubular epithelial cells)
In Vivo Model	For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium(30 mg/kg). Then, UUO surgery orsham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10% DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10% DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium (30 mg/kg). Then, UUO surgery or sham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10 % DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10 % DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. Click to Show/Hide
Response Description	Formononetin (FN) alleviates chronic kidney disease (CKD) by impeding ferroptosis-associated fibrosis by suppressing the Smad3/ATF3/SLC7A11 signaling and could serve as a candidate therapeutic drug for CKD. In addition, FN also promoted the separation of the Nrf2/Keap1 complex and enhanced Nrf2 nuclear accumulation.

Mitogen-activated protein kinase 8 (MAPK8)

Regulator Info

Status epilepticus [ICD-11: 8A66]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[13]
Regulator for Ferroptosis	Driver
Responsed Drug	Seratrodast		Discontinued in Phase 3	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated. Click to Show/Hide
Response Description	Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures.

Mitogen-activated protein kinase 1 (MAPK1)

Regulator Info

Corpus uteri cancer [ICD-11: 2C76]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[14]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Simvastatin		Investigative	Drug Info
Pathway Response	MAPK signaling pathway			hsa04010
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Ishikawa cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
Response Description	Simvastatin has the potential to be a targeted drug for endometrial cancer (EC) treatment. Besides, the inhibition to the RAS/MAPK signaling pathway allows simvastatin to induce ferroptosis through up-regulating the level of ROS, MDA, Fe2+, and TRF1 (TF) and reducing the level of GSH, SLC7A11, and FPN in cells.

LINC00618 (IncRNA)

Regulator Info

Myeloid leukaemia [ICD-11: 2B33]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[15]
Regulator for Ferroptosis	Driver
Responsed Drug	Vincristine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
Response Description	LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment. Furthermore, LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11).

Krueppel-like factor 4 (KLF4)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[16]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Polyphyllin III		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Hs-578T cells	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	HBL-100 cells	Normal	Homo sapiens	CVCL_4362
	BT-549 cells	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MDA-MB-453 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0418
In Vivo Model	MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 10⁶ cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm³, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day. Click to Show/Hide
Response Description	Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis.

Krueppel-like factor 15 (KLF15)

Regulator Info

Cardiomyopathy [ICD-11: BC43]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[17]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Elabela	Investigative	Drug Info
Pathway Response	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	rAFs (Rat adventitial fibroblasts)
Response Description	KLF15 siRNA impeded the beneficial roles of elabela (ELA) in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders.

hsa-miR-489-3p (miRNA)

Regulator Info

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[18]
Regulator for Ferroptosis	Driver
Responsed Drug	Levobupivacaine		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	GES-1 cells	Normal	Homo sapiens	CVCL_EQ22
	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
	SGC-7901 cells	Gastric carcinoma	Homo sapiens	CVCL_0520
In Vivo Model	Ten SCID nude mice aged 6-8 weeks were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China), and subcutaneously injected with SGC7901 cells (5 x 10⁶ cells per mouse) in left back. One week after feeding, the mice were randomly divided into two groups, the control and treatment group. For the next 25 days, the mice in treatment group were injected with erastin (15 mg/kg intraperitoneally) or co-treated with 40 mol/kg body weight of levobupivacaine once a day. The body weight and tumor size were measured every 3 days. Click to Show/Hide
Response Description	Levobupivacaine-upregulated miR-489-3p enhanced ferroptosis of gastric cancer cells by targeting SLC7A11. MiR-489-3p was involved in levobupivacaine-induced ferroptosis of gastric cancer cells. Levobupivacaine/miR-489-3p/SLC7A11 axis attenuates gastric cancer cell proliferationin vitro.

hsa-miR-382-5p (miRNA)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[19]
Regulator for Ferroptosis	Driver
Responsed Drug	Lidocaine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
In Vivo Model	SPF-level male nude mice aged 56weeks and weighted around 20 g were purchased from Vitalriver (China). All mice were maintained in a 12-hour circadian rhythm, and had free access to water and food. Cancer cells were subcutaneously injected into the right flank of mice. Lidocaine was administrated to mice at a dose of 1.5 mg per kg injected through the vail tails. For control group, the mice were treated with saline. Tumor volume and mice body weight were monitored every 5 days. Click to Show/Hide
Response Description	The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells.

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[19]
Regulator for Ferroptosis	Driver
Responsed Drug	Lidocaine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
In Vivo Model	SPF-level male nude mice aged 56weeks and weighted around 20 g were purchased from Vitalriver (China). All mice were maintained in a 12-hour circadian rhythm, and had free access to water and food. Cancer cells were subcutaneously injected into the right flank of mice. Lidocaine was administrated to mice at a dose of 1.5 mg per kg injected through the vail tails. For control group, the mice were treated with saline. Tumor volume and mice body weight were monitored every 5 days. Click to Show/Hide
Response Description	The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells.

hsa-miR-122-5p (miRNA)

Regulator Info

Intracerebral hemorrhage [ICD-11: 8B00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[20]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Isorhynchophylline		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	p53 signaling pathway			hsa04115
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection). Click to Show/Hide
Response Description	Isorhynchophylline (IRN) decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. In conclusion, IRN protects neurocyte from intracerebral hemorrhage (ICH)-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH.

Gap junction alpha-1 protein (GJA1)

Regulator Info

Acute kidney failure [ICD-11: GB60]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[21]
Regulator for Ferroptosis	Driver
Responsed Drug	GAP 27		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Glutathione metabolism			hsa00480
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
In Vivo Model	Thirty-two male C57BL/6 mice (20 ± 2) g (Beijing Weitonglihua Experimental Animal Technology Co., Ltd.) were bred in individually ventilated cages (IVC) at SPF conditions, kept on a 12 h light/dark cycle, relative humidity conditions (40-70%) and controlled temperature (24 ± 2 ). After one-week acclimation mice were divided randomly into four groups: control group, cisplatin group (20 mg/kg cisplatin dissolved in saline), cisplatin + Fer-1 group (5 mg/kg Fer-1 dissolved in DMSO), and cisplatin + gap27 group (35 ug/kg gap27 dissolved in DMSO). There were eight animals in each group and 20 mg/kg cisplatin was given to each animal once by intraperitoneal injection except mice in the control group. Fer-1 and gap27 was administered 1 h before the injection of cisplatin. Click to Show/Hide
Response Description	Downregulation of Cx43 expression by gap27 reduced acute kidney injury in the animal model by inhibiting cisplatin-induced ferroptosis. Therefore, our results indicated that downregulation of Cx43 can inhibit ferroptosis by restoring the level of SLC7A11 in the system xctransporter and alleviate cisplatin-induced acute kidney injury.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[21]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
In Vivo Model	Thirty-two male C57BL/6 mice (20 ± 2) g (Beijing Weitonglihua Experimental Animal Technology Co., Ltd.) were bred in individually ventilated cages (IVC) at SPF conditions. After one-week acclimation mice were divided randomly into four groups: control group, cisplatin group (20 mg/kg cisplatin dissolved in saline), cisplatin + Fer-1 group (5 mg/kg Fer-1 dissolved in DMSO), and cisplatin + gap27 group (35 ug/kg gap27 dissolved in DMSO). There were eight animals in each group and 20 mg/kg cisplatin was given to each animal once by intraperitoneal injection except mice in the control group. Fer-1 and gap27 was administered 1 h before the injection of cisplatin. Click to Show/Hide
Response Description	Downregulation of Cx43 ( GJA1) can inhibit ferroptosis by restoring the level of SLC7A11 in the system xctransporter and alleviate cisplatin-induced acute kidney injury. And downregulating Cx43 not only inhibits ferroptosis, but also inhibits apoptosis.

Endothelial PAS domain-containing protein 1 (EPAS1)

Regulator Info

Degenerative arthritis [ICD-11: FA05]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[22]
Regulator for Ferroptosis	Driver
Responsed Drug	D-Mannose	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hCDs (Chondrocytes)
In Vivo Model	C57BL/6 J mice (8 weeks old, female) were purchased from Dossy Experimental Animal Limited Company (Chengdu, China). For surgery, mice were anaesthetized with pentobarbital sodium (100 mg/kg, injected intraperitoneally) and subjected to unilateral ACLT procedures. 28 The sham group received a skin incision and suturing without patellar dislocation or ligament transection. For virus injection, mice were intraarticularly injected with 1 x 10⁹ pfu (8 ul) of mock or AdEpas1 virus after one week of surgery. For Fer1 (MCE, Monmouth Junction, HY100579) injection, mice were intraarticularly injected with 1 mg/kg Fer1 or with vehicle two weeks after surgery, the injection was repeated once a week. Click to Show/Hide
Response Description	D-mannose alleviates osteoarthritis (OA) progression by suppressing HIF-2a-mediated chondrocyte sensitivity to ferroptosis. Overexpression of HIF-2a in chondrocytes by Ad- Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. Also, the RNA and protein levels of the two key ferroptosis suppressors, Gpx4 and Slc7a11, were increased in Dmannosetreated chondrocytes.

Cyclic GMP-AMP synthase (CGAS)

Regulator Info

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[23]
Regulator for Ferroptosis	Driver
Responsed Drug	Niraparib		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Cytosolic DNA-sensing pathway			hsa04623
Cell Process	Cell ferroptosis
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
	MC-38 cells	Colon adenocarcinoma	Homo sapiens	CVCL_B288
In Vivo Model	Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 10⁶) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm³, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed. Click to Show/Hide
Response Description	Niraparib, a widely used PARPi, augmented cGAS-mediated ferroptosis and immune activation. In colorectal cancer models, cGAS signaling exerts tumor control via ATF3SLC7A11GPX4-mediated ferroptosis and IFNCD8 T cell-mediated antitumor immune response.

Cyclic AMP-dependent transcription factor ATF-3 (ATF3)

Regulator Info

Glioblastoma [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[24]
Regulator for Ferroptosis	Driver
Responsed Drug	Brucine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	U118 cells	Astrocytoma	Homo sapiens	CVCL_0633
	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
	A-172 cells	Glioblastoma	Homo sapiens	CVCL_0131
In Vivo Model	The athymic BALB/c nude mice (4 weeks; 20-22 g; Beijing Vital River Laboratory Animal Technology Company, China) were housed in a specific pathogen-free environment under a 12-h lightdark cycle with free access to food and water. The animals were allowed to acclimatize to their surroundings for 3 days. U87 cells (1 x 10⁶) in the logarithmic growth phase in 100 uL PBS were subcutaneously injected into the right flank. Therapeutic experiments were started when the tumor reached around 150 mm³ after about 10 days. Mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 6) or 40 mg/kg bodyweight (n = 6) in the same volume (50 uL) once a day for 13 times. Click to Show/Hide
Response Description	Brucine inhibited glioma cell growth in vitro and in vivo, and brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT (SLC7A11) to prevent H2O2 degradation on the other hand.

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[12]
Regulator for Ferroptosis	Driver
Responsed Drug	Formononetin	Investigative	Drug Info
Pathway Response	Ferroptosis		hsa04216
	Fatty acid metabolism		hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mPRTECs (Mouse primary renal tubular epithelial cells)
In Vivo Model	For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium(30 mg/kg). Then, UUO surgery orsham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10% DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10% DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium (30 mg/kg). Then, UUO surgery or sham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10 % DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10 % DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. Click to Show/Hide
Response Description	Formononetin (FN) alleviates chronic kidney disease (CKD) by impeding ferroptosis-associated fibrosis by suppressing the Smad3/ATF3/SLC7A11 signaling and could serve as a candidate therapeutic drug for CKD. In addition, FN also promoted the separation of the Nrf2/Keap1 complex and enhanced Nrf2 nuclear accumulation.

Cellular tumor antigen p53 (TP53)

Regulator Info

Glioblastoma [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[25]
Regulator for Ferroptosis	Driver
Responsed Drug	Pseudolaric acid B		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	U-87MG cells	Glioblastoma	Homo sapiens	CVCL_0022
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
	SHG-44 cells	Astrocytoma	Homo sapiens	CVCL_6728
In Vivo Model	Twenty athymic BALB/c nude mice (aged 4 weeks, weight 20-22 g, from Shanghai laboratory animal Center, Shanghai, China) were housed in a specific pathogen-free environment. A total of 1 x 10⁶ logarithmically growing C6 cells in 100 uL of PBS were subcutaneously injected into the right flank of each mouse. Therapeutic experiments were started when the tumor reached about 150 mm³ after about 7 days. The mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 5/group), PAB at the dosage of 10 mg/kg body weight (n = 10/group) and 20 mg/kg body weight (n = 10/group) in the same volume 50 uL once a days for 8 times. Click to Show/Hide
Response Description	Pseudolaric acid B (PAB) improved intracellular iron by upregulation of transferrin receptor. The increased iron activated Nox4, which resulted in overproduction of H2O2and lipid peroxides. Moreover, PAB depleted intracellular GSH via p53-mediated xCT (SLC7A11) pathway, which further exacerbated accumulation of H2O2and lipid peroxides. Thus, PAB triggers ferroptosis in glioma cells and is a potential medicine for glioma treatment.

T-cell lymphoma [ICD-11: 2B01]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[26]
Regulator for Ferroptosis	Driver
Responsed Drug	Kayadiol		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	YT cells	Natural killer cell lymphoblastic leukemia	Homo sapiens	CVCL_1797
	hPBLs (Human peripheral blood lymphocytes)
Response Description	Kayadiol decreased the expression of SLC7A11 and GPX4, the negative regulatory proteins for ferroptosis. And p53 was the key mediator of kayadiol-induced ferroptosis by SLC7A11/GPX4 axis through p53 knockout experiments. Kayadiol can serve as an effective alternative in the treatment of NK/T cell lymphoma.

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[4]
Regulator for Ferroptosis	Driver
Responsed Drug	Bavachin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MG-63 cells	Osteosarcoma	Homo sapiens	CVCL_0426
In Vitro Model	HOS cells	Osteosarcoma	Homo sapiens	CVCL_0312
Response Description	Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression.

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[27]
Regulator for Ferroptosis	Driver
Responsed Drug	Tanshinone IIA		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	BGC-823 cells	Gastric carcinoma	Homo sapiens	CVCL_3360
	NCI-N87 cells	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
In Vivo Model	All mice were housed under a setting of 12-h light/dark cycle at 22 ± 1, 55% humidity and fed with water and food provided at regular time. During the entire maintenance period, all mice were permitted free cage activity without joint immobilization. The initial body weights of the mice were between 20 and 23 grams. After subcutaneous injection of 2 x 10⁶ BGC-823 gastric cancer cells into the back of NOD-SCID mice, the mice were treated with or without Tan IIA (50 mg/kg) or Tan IIA in combination with Fer-1 (50 mg/kg). Tan IIA was diluted in DMSO:Methanol:Hydroxypropyl-b-cydodextrin (HP-b-CD) = 1:1:1. Fer-1 was also dissolved in DMSO:Methanol:HP-b-CD. Seven days after BGC-823 gastric cancer cells injection, intraperitoneal injection with Tan IIA was carried out every other day followed by killing at day 22 of tumor cell inoculation. All mice were killed by dislocation of the cervical vertebrae. Before killing, the tumor volume was measured every 3 days. All experiments were carried out using six mice each group in three independent experiments of a time-dependent manner with three time points. Click to Show/Hide
Response Description	Tanshinone IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT (SLC7A11) expression. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis.

Melanoma [ICD-11: 2C30]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[28]
Regulator for Ferroptosis	Driver
Responsed Drug	Gambogenic Acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Cell adhesion molecules			hsa04514
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	A-375 cells	Amelanotic melanoma	Homo sapiens	CVCL_0132
	A2058 cells	Amelanotic melanoma	Homo sapiens	CVCL_1059
Response Description	Gambogenic acid (GNA) significantly inhibited the invasion, migration and EMT in melanoma cells, and these cells exhibited small mitochondrial wrinkling (an important feature of ferroptosis). GNA upregulated the expression of p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the model cells, contributing to the mechanisms underlying GNA-induced ferroptosis.

Parkinson disease [ICD-11: 8A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[29]
Regulator for Ferroptosis	Driver
Responsed Drug	Cyperquat		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC12 cells	Adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481
Response Description	As a classic drug employed inin vitromodels of Parkinson's disease, 1-methyl-4-phenylpyridinium (MPP) can induce senescence in PC12 cells. The expression of the ferroptosis-related proteins ASCL4 was upregulated and FTH1 was downregulated, which promoted accumulation of lipid peroxides and eventually led to ferroptosis. By rescuing MPP-induced ferroptosis, cell senescence could be inhibited, and its molecular mechanism was related to a p53/SLC7A11/GPX4 signaling pathway.

Status epilepticus [ICD-11: 8A66]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[13]
Regulator for Ferroptosis	Driver
Responsed Drug	Seratrodast		Discontinued in Phase 3	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated. Click to Show/Hide
Response Description	Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures in Epilepsy.

Intracerebral hemorrhage [ICD-11: 8B00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[20]
Regulator for Ferroptosis	Driver
Responsed Drug	Isorhynchophylline		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	p53 signaling pathway			hsa04115
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection). Click to Show/Hide
Response Description	Isorhynchophylline (IRN) decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. In conclusion, IRN protects neurocyte from intracerebral hemorrhage (ICH)-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH.

Sarcopenia [ICD-11: FB32]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[30]
Regulator for Ferroptosis	Driver
Responsed Drug	Ferric citrate		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Glutathione metabolism			hsa00480
Cell Process	Cell ferroptosis
In Vitro Model	C2C12 cells	Normal	Mus musculus	CVCL_0188
In Vivo Model	The 8-week- and 40-week-old male SAMP8 mice were purchased from the model animal research center of Zhishan Institute of Healthcare Research Co., Ltd. (Beijing, China). All the mice were kept in an SPF grade animal facility at 24 with a relative humidity of 50%-60%, and in a light/dark cycle of 12 h/12 h. Click to Show/Hide
Response Description	Ferric citrate induced ferroptosis in C2C12 cells, as well as impaired their differentiation from myoblasts to myotubes. Iron overload upregulated the expression of P53, which subsequently repressed the protein level of Slc7a11 (solute carrier family 7, member 11), a known ferroptosis-related gene. Targeting iron accumulation and ferroptosis might be a therapeutic strategy for treating sarcopenia.

Lung injury [ICD-11: NB32]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[50]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HBE1 cells	Normal	Homo sapiens	CVCL_0287
In Vivo Model	For the models of CS and LPS exposure, mice were anesthetized and intratracheally instilled with CS suspensions (3 mg/50 ul) or LPS (1 mg/kg). For the models of CS + Ferr-1/DFO, mice were intraperitoneally injected with Ferr-1 (1.25 umol/kg) or intranasal instilled with DFO (10 mg/kg) for 7 consecutive days after CS instillation. For the models of LPS + Ferr-1/DFO, mice were pretreated with Ferr-1 or DFO for 2 consecutive days and then intratracheally instilled with LPS. Mice were sacrificed 24 h after LPS instillation. For the X-ray exposure model, mice were exposed to ionizing radiation (IR) at 20 Gy, which was delivered at the dose rate of 2 Gy/min and a source skin distance of 51 cm by an X-ray generator (Model X-RAD320iX; Precision X-Ray, Inc., North Branford, CT, USA), and sacrificed 3 days after radiation. Click to Show/Hide
Response Description	STAT6 negatively regulates ferroptosis through competitively binding with CBP, which inhibits P53 acetylation and transcriptionally restores SLC7A11 expression. Finally, pulmonary-specific STAT6 overexpression decreased the ferroptosis and attenuated CS and LPS induced acute lung injury.

CD44 antigen (CD44)

Regulator Info

Colorectal cancer [ICD-11: 2B91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[31]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Sodium butyrate		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	FHC cells	Normal	Homo sapiens	CVCL_3688
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
In Vivo Model	Six-week-old male C57BL/6J mice were purchased from the Medical Laboratory Animal Center of Guangdong Province (Foshan, China). Forty-five C57BL/6L mice were randomized into 4 groups after 1 week of adaptive feeding: (1) Control group (n = 9); (2) AOM/DSS group (n = 12); (3) AOM/DSS + NaB (orally) group (n = 12); 4) AOM/DSS + NaB (intraperitoneal injection) group (n = 12). The Control group received an intraperitoneal injection of saline solution beginning on day 1, and received sterile drinking water throughout the study. Other three groups received an intraperitoneal injection of 10 mg/kg AOM (Sigma Aldrich) beginning on day 1, and received drinking water containing 2.5% DSS at the second and eighth weeks (2% DSS in the fifth week). Besides, 0.1 M NaB (Sigma Aldrich) was given in drinking water during the whole experiment process in AOM/DSS + NaB (p.o.) group, while AOM/DSS + NaB (i.p.) group was injected intraperitoneally (IP) with 1 g/kg NaB per day. Click to Show/Hide
Response Description	Sodium butyrate (NaB) induces ferroptosis in colorectal cancer cells through the CD44/SLC7A11 signaling pathway and has synergistic effects with Erastin.

Injury of intra-abdominal organs [ICD-11: NB91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[37]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
	Ubiquitin mediated proteolysis	hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	mPHs (Mouse primary hepatocytes)
In Vivo Model	ALI induction was performed in 6-8-week-old age-matched C57BL/6J male mice (n = 10-12 per group) by intraperitoneal injection of 3 mL/kg CCl4 in coconut oil. Control and negative control mice were injected with PBS and coconut oil, respectively. At 6 h after injection of CCl4, mice were divided into three groups: CCl4 group, injected with 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; CCl4 + MSC group, injected with 5 x 10⁵ MSCs suspended in 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; CCl4 + Fer-1 group, intraperitoneally injected with ferrostatin-1 (Fer-1, a ferroptosis inhibitor, 2.5 umol/kg body weight). Erastin, intraperitoneal injection of erastin (a ferroptosis inducer, 30 mg/kg body weight) twice every other day, and then the mice were divided into two groups (n = 10-12 per group): Erastin group, injected with 100 uL PBS (supplemented with 2% mouse serum) through a tail vein; Erastin + MSC group, injected with 5 x 10⁵ MSCs suspended in 100 uL PBS (supplemented with 2% mouse serum) through the tail vein. Click to Show/Hide
Response Description	MSC-Exo protected against CCl4-induced acute liver injury (ALI) through inhibiting hepatocyte ferroptosis via restoring the SLC7A11 protein level. Additionally, the exosome-induced recovery of SLC7A11 protein was accompanied by upregulations of CD44 and OTUB1.

Health [ICD-11: N.A.]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[145]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	HEK293 cells	Normal	Homo sapiens	CVCL_0045
	SK-N-BE(2)-C cells	Neuroblastoma	Homo sapiens	CVCL_0529
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SK-RC-42 cells	Renal cell carcinoma	Homo sapiens	CVCL_6192
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	T24 cells	Bladder carcinoma	Homo sapiens	CVCL_0554
	UM-UC-3 cells	Bladder carcinoma	Homo sapiens	CVCL_1783
	SW780 cells	Bladder carcinoma	Homo sapiens	CVCL_1728
In Vivo Model	5.0 x 10⁶ cells were mixed with Matrigel (BD Biosciences) at 1:1 ratio (v/v) and injected subcutaneously into seven-week old nude mice (NU/NU; Charles River). Mice were fed with regular chow. After nine weeks, the mice were killed and the tumors were weighed and recorded. Click to Show/Hide
Response Description	Overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner.

Bromodomain-containing protein 4 (BRD4)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[32]
Regulator for Ferroptosis	Suppressor
Responsed Drug	JQ1		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell autophagy
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Hs-578T cells	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	MCF-10A cells	Normal	Homo sapiens	CVCL_0598
In Vivo Model	Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 10⁷ cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. Click to Show/Hide
Response Description	Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression.

5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)

Regulator Info

Colon cancer [ICD-11: 2B90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[33]
Regulator for Ferroptosis	Driver
Responsed Drug	Sulfasalazine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
Cell Process	Cell autophagy
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	Calu-1 cells	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	To generate murine subcutaneous tumors, 5 x 10⁶ HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 10⁶ KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female). Click to Show/Hide
Response Description	BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/ AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib) in Colon carcinoma.

5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)

Regulator Info

Multiple myeloma [ICD-11: 2A83]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[34]
Regulator for Ferroptosis	Driver
Responsed Drug	Fingolimod		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	U266B1 cells	Plasma cell myeloma	Homo sapiens	CVCL_0566
	RPMI-8226 cells	Plasma cell myeloma	Homo sapiens	CVCL_0014
Response Description	Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Fingolimod (FTY720) can activate PP2A subunit C and dephosphorylate AMPKa, and then inhibit the expression of SLC7A11 and GPX4. In conclusion, FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway.

Uc.339 (IncRNA)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[35]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
	Glutathione metabolism			hsa00480
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell metastasis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	16HBE14o- cells	Normal	Homo sapiens	CVCL_0112
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In Vivo Model	6-8 weeks mice were divided into 4 groups randomly. Mice were injected with 2.5 x 10⁵ wild type LLC cells, Uc.339 OE-LLC cells, with or without miR-339 inhibitors, respectively, through the lateral tail vain. The mice were killed after 4 weeks by carbon dioxide asphyxiation followed by cervical dislocation to ensure death. The lungs were removed, rinsed with PBS, and the number of metastatic foci on the lung surface was counted. The pulmonary lobes were subsequently kept in 4% paraformaldehyde for later paraffin embedding and hematoxylin and eosin staining. Click to Show/Hide
Response Description	LncRNA Uc.339 competitively binds to pri-miR-339 and inhibits the production of mature miR-339. At the same time, it is the first to clarify the reason for the negative correlation between miR-339 and SLC7A11 expression in lung cancer, and for the first verification that the inhibition of miR-339 led to increased expression of SLC7A11 and weakens ferroptosis, which constituted an important carcinogenesis mechanism for lung adenocarcinoma metastasis.

Tripartite motif-containing protein 26 (TRIM26)

Regulator Info

Liver fibrosis [ICD-11: DB93]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[38]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	LX-2 cells	Normal	Homo sapiens	CVCL_5792
In Vivo Model	A total of 24 C57BL/6 mice were obtained from the Sippr-BK laboratory animal Co., Ltd. (Shanghai, China). They were randomly divided into four groups: Group I, Vehicle (control); Group II, CCl4; Group III, CCL4 + Vector; Group IV, CCL4 + oeTRIM26. Liver fibrosis was induced in Groups II - IV, by intraperitoneally injecting 50% carbon tetrachloride (CCl4) in corn oil (0.1 mL/100 g body weight) over 8 weeks (3 times/week); control mice were injected with corn oil only. Then, recombinant adenovirus Vector or oeTRIM26 (5 x 10⁹ pfu/mouse, 0.5 mL) was injected into the mice of Group III or IV, respectively, through the tail vein. Click to Show/Hide
Response Description	TRIM26 promotes HSCs ferroptosis to suppress liver fibrosis through mediating the ubiquitination of SLC7A11. The TRIM26-targeted SLC7A11 suppression can be a novel therapeutic strategy for liver fibrosis.

Transforming growth factor beta-1 proprotein (TGFB1)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[39]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PLC/PRF/5 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0485
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SNU-387 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0250
	SNU-449 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
	SNU475 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0497
	SK-HEP-1 cells	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
	HuH-6 cells	Hepatoblastoma	Homo sapiens	CVCL_4381
Response Description	TGF-B1 represses xCT (SLC7A11) expression via Smad3 activation and enhances lipid peroxidation in hepatocellular carcinoma cells with an early TGF-B1 signature, which would benefit from the targeting of GPX4.

Transcriptional coactivator YAP1 (YAP1)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[40]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Hippo signaling pathway			hsa04390
Cell Process	Cell ferroptosis
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	SNU-398 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HLE cells	Hepatocellular carcinoma	Homo sapiens	CVCL_1281
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
In Vivo Model	SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (10⁶ in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks. Click to Show/Hide
Response Description	In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression.

Transcription factor Sp1 (SP1)

Regulator Info

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[42]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MPC-5 cells	Normal	Mus musculus	CVCL_AS87
In Vivo Model	Male C57BL/6 mice (6-8 weeks old, 20-25 g) were obtained from KCI BioTech (Jiangsu, China. Mice were intraperitoneally injected 50 mg/kg/day of STZ for 5 straight days to generate DN mouse. At 3 days post injection, glucose levels were measured from tail blood, and blood glucose level more than 16.4 mmol/L indicated that DN models was established. Click to Show/Hide
Response Description	Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced diabetic nephropathy mice.

Transcription factor SOX-2 (SOX2)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[43]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hTCs (Human tumour cells)
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
In Vivo Model	Mice were housed in the SIBCB animal facility under SPF conditions with a 12 hours light/dark cycle at room temperature. For Erastin treatment, we sequentially dissolved Erastin in 5% DMSO, 30% PEG300, 5% Tween80 and ddH2O according to the manufacturers instructions, it should be noted that the solvent needed to be added from left to right, after the dissolution was completely clear, added the next reagent, 40 mg/kg Erastin was intraperitoneal injected, every other day for 2 weeks. For IKE treatment, 50 mg/kg IKE was intraperitoneal injected, once a day for 2 weeks. Click to Show/Hide
Response Description	Tumors with high SOX2 expression were more resistant to ferroptosis, and SLC7A11 expression was positively correlated with SOX2 in both mouse and human lung cancer tissue. This study uncovers a SOX2-SLC7A11 regulatory axis that confers resistance to ferroptosis in lung cancer stem-like cells.

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[44]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mKTs (Mouse knee tissues)
	HK-2 (Human renal glomerular endothelial cells)
In Vivo Model	All C57BL/6 mice (5-6 weeks, 18-20 g) were obtained from Animal Testing Center of Qinglongshan (Nanjing, Suzhou, China). DN mice were fed with a high-fat diet (HFD) for 12 weeks and then injected with STZ (30 mg/kg of streptozotocin; Sigma-Aldrich, St Louis, MO, USA) i.p. for 7 consecutive days. Blood glucose levels of mice were measured using 16.7 mmol/l after one week of the final injection. Then, mice were killed under anesthesia and their kidneys taken for analysis after induction of STZ at 4 months. Click to Show/Hide
Response Description	Circular RNA circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/ SLC7A11 by miR-770-5p. Importantly, this research indicated that circ ASAP2 might act as a target for improving the role of ferroptosis in diabetes nephropathy.

Transcription factor AP-2 gamma (TFAP2C)

Regulator Info

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[45]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	22Rv1 cells	Prostate carcinoma	Homo sapiens	CVCL_1045
In Vivo Model	PC3 and PC3/DR cells (5 x 10⁶ cells) were subcutaneously injected into each flank of six-week-old male BALB/c nude mice (HFK Biotech, China). When the tumor volume reached 100 mm³, the mice were treated with Dimethyl Sulfoxide (DMSO) alone, DTX (5 mg/kg body weight, every two days) with DMSO or erastin (20 mg/kg body weight in 20 ul DMSO plus 130 ul corn oil, daily) by intraperitoneal injection. Click to Show/Hide
Response Description	Docetaxel (DTX)-resistant prostate cancer cells develop tolerance toward ferroptosis and that lncRNAPCAT1 promotes chemoresistance by blocking DTX-induced ferroptosis. Mechanistic studies indicated that PCAT1 activates the expression of SLC7A11 by interacting with c-Myc and sponging with miR-25-3p. In addition, TFAP2C activates PCAT1 expression to reduce ferroptosis susceptibility and enhance chemoresistance.

Toll-like receptor 4 (TLR4)

Regulator Info

Preeclampsia [ICD-11: JA24]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[46]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hPTs (Human placental tissues)
Response Description	Panx1 and TLR4 are suggested to induce ferroptosis in Preeclampsia via SLC7A11-mediated signaling pathways, offering a novel perspective on PE pathogenesis and novel diagnostic tools for Preeclampsia.

Telomerase reverse transcriptase (TERT)

Regulator Info

Lung injury [ICD-11: NB32]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[47]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
In Vivo Model	We received 60 C57BL/6J mice and 48 Nrf2 knockout (Nrf2-/-) mice of the same genetic background from the RIKEN Bio-Resource Centre via the National BioResource Project, MEXT, Japan. Intestinal ischemia was simulated by clamping the superior mesenteric artery following the intraperitoneal administration of 50 mg/kg sodium pentobarbital. Forty-five minutes later, the intestine was allowed to re-perfuse for 3 h. Click to Show/Hide
Response Description	Nrf2 can negatively regulate ferroptosis via modulation of TERT and SLC7A11 levels. Overexpression of TERT (OETERT) alleviates ferroptosis via modulation of SLC7A11. The conclusion from this study brings insight into new candidates that can be targeted in future ischemia/reperfusion-induced acute lung injury (IIR-ALI) therapy.

Tafazzin (TAFAZZIN)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[40]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Hippo signaling pathway			hsa04390
Cell Process	Cell ferroptosis
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	SNU-398 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HLE cells	Hepatocellular carcinoma	Homo sapiens	CVCL_1281
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
In Vivo Model	SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (10⁶ in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks. Click to Show/Hide
Response Description	In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression.

SNHG14 (IncRNA)

Regulator Info

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[48]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	SJSA-1 cells	Osteosarcoma	Homo sapiens	CVCL_1697
Response Description	LncRNA SNHG14 targeted and down-regulated the expression of miR-206, further affecting the common ferroptosis inhibitor SLC7A11, and preventing NR-SJSA1 cells from undergoing ferroptosis. In conclusion, our findings highlight the involvement of lncRNA SNHG14 in ferroptosis and chemotherapy resistance of nutlin3a-resistant NR-SJSA1 cells, thus shedding new insight on how to overcome drug resistance in osteosarcoma cells and improve treatment efficacy.

SLC16A1-AS1 (IncRNA)

Regulator Info

Hereditary Leiomyomatosis [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[49]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
Response Description	SLC16A1-AS1 served as a sponge of miR-143-3p, and knockdown SLC16A1-AS1 significantly increased the enrichment of miR-143-3p. And then, SLC7A11 was identified as the target protein of miR-143-3p, and overexpression miR-143-3p remarkably inhibited the expression of SLC7A11. And silencing lncRNA SLC16A1-AS1 can induce ferroptosis through miR-143-3p/SLC7A11 signaling in renal cell carcinoma.

Signal transducer and activator of transcription 6 (STAT6)

Regulator Info

Lung injury [ICD-11: NB32]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[50]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HBE1 cells	Normal	Homo sapiens	CVCL_0287
In Vivo Model	For the models of CS and LPS exposure, mice were anesthetized and intratracheally instilled with CS suspensions (3 mg/50 ul) or LPS (1 mg/kg). For the models of CS + Ferr-1/DFO, mice were intraperitoneally injected with Ferr-1 (1.25 umol/kg) or intranasal instilled with DFO (10 mg/kg) for 7 consecutive days after CS instillation. For the models of LPS + Ferr-1/DFO, mice were pretreated with Ferr-1 or DFO for 2 consecutive days and then intratracheally instilled with LPS. Mice were sacrificed 24 h after LPS instillation. For the X-ray exposure model, mice were exposed to ionizing radiation (IR) at 20 Gy, which was delivered at the dose rate of 2 Gy/min and a source skin distance of 51 cm by an X-ray generator (Model X-RAD320iX; Precision X-Ray, Inc., North Branford, CT, USA), and sacrificed 3 days after radiation. Click to Show/Hide
Response Description	STAT6 negatively regulates ferroptosis through competitively binding with CBP, which inhibits P53 acetylation and transcriptionally restores SLC7A11 expression. Finally, pulmonary-specific STAT6 overexpression decreased the ferroptosis and attenuated CS and LPS induced acute lung injury.

Sentrin-specific protease 1 (SENP1)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[3]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 10⁶ cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. Click to Show/Hide
Response Description	SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy.

SEMA5A-IT1 (IncRNA)

Regulator Info

Ischemia/reperfusion injury [ICD-11: DB98]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[52]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	AC16 [Human hybrid cardiomyocyte] cells	Normal	Homo sapiens	CVCL_4U18
Response Description	SEMA5A-IT1 overexpression upregulated the expression of BCL2 and SLC7A11 through sponging miR-143-3p, thereby protecting cardiomyocytes against apoptotic and ferroptosis cell death. In conclusion, we propose that SEMA5A-IT1, which is transported to cardiomyocytes through circulating sEVs, is an important regulatory molecule that protects cardiomyocytes from ischemia-reperfusion injury.

RNA-binding protein PNO1 (PNO1)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[53]
Regulator for Ferroptosis	Suppressor
Pathway Response	Autophagy			hsa04140
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Xenograft mouse model experiments were used male BALB/c nude mice (4 weeks old) purchased from SPF Biotechnology (Beijing, China). Each mouse was injected 5 x 10⁶ tumor cells at the volume of 100 uL into the subcutaneous tissue. The tumor volume and weight of the mice was observed every 2 days. Mice were monitored daily and the tumor volume calculated according to the equation volume = length x width2 x 1/2. Click to Show/Hide
Response Description	PNO1 inhibits autophagy-mediated ferroptosis via GSH metabolic reprogramming as demonstrated above. We also demonstrated that PNO1 inhibition repressed SLC7A11 through p53 to promote ferroptosis. These observations suggested that sh-PNO1 could be a new target in hepatocellular carcinoma therapy.

Protein mono-ADP-ribosyltransferase PARP9 (PARP9)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP9 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP9 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP8 (PARP8)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP8 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP8 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP6 (PARP6)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP6 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP6 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP4 (PARP4)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP4 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP4 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP3 (PARP3)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP3 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP3 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP16

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP16 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP16 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP15

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP15 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP15 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP14

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP14 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP14 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP12

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP12 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP12 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP11 (PARP11)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP11 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP11 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Protein mono-ADP-ribosyltransferase PARP10 (PARP10)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP10 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP10 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Poly [ADP-ribose] polymerase 2 (PARP2)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP2 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP2 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

Poly [ADP-ribose] polymerase 1 (PARP1)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HEY cells	Ovarian carcinoma	Homo sapiens	CVCL_0297
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Female 4- to 6-week-old BALB/c nude mice were purchased from SLA Laboratory Animal (Changsha, China) and housed in a specific pathogen-free facility. 2 x 10⁶ A2780 or 1 x 10⁶ HEY cells were injected subcutaneously into mice to grow tumors up to approximately 100 mm³. Mice were then intraperitoneally injected olaparib (100 mg/kg) or/and liproxstatin-1 (10 mg/kg, A2780) or/and sulfasalazine (250 mg/kg, HEY) until the endpoint indicated in the corresponding figures. Click to Show/Hide
Response Description	Mechanistically, pharmacological inhibition or genetic deletion of PARP1 downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Pharmacologic inhibition of PARP1 is the primary therapeutic strategy for BRCA mutant ovarian cancer.

PMAN (IncRNA)

Regulator Info

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[55]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	AGS cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MGC-803 cells	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
In Vivo Model	For animal models of gastric subserosal injection, we collected MGC-803 cell lines (5 x 10 cells) that were infected by lentivirus with or without PMAN-OE, and suspended in 40 ul serum-free medium (50% Matrigel). After that, nude mice (six mice per group) were anesthetized by intraperitoneal injection of 100 ul of pentobarbital (1%). After disinfection, the abdominal cavity was opened to expose the greater curvature of the stomach. The tumor suspension (40 ul) was implanted under the serosa of the greater curvature of the stomach of the nude mice through an insulin needle. Click to Show/Hide
Response Description	HIF-1 could act as a protective factor against ferroptosis in gastric cancer (GC) cells. HIF-1 activates PMAN at the transcriptional level, which greatly improves the output of ELAVL1 in the cytoplasm. ELAVL1 directly combines with the AREs of SLC7A11 mRNA 3-UTR and improves the stability ofSLC7A11mRNA, thereby increasing the expression of SLC7A11 and reducing the accumulation of ROS and iron in ferroptosis, ultimately promoting the proliferation and development of tumor cells.

Platelet-derived growth factor receptor alpha (PDGFRA)

Regulator Info

Glioblastoma [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[56]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	HEB (Human glial cells)
	SF126 cells	Glioblastoma	Homo sapiens	CVCL_1688
	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
In Vivo Model	4-week-old female BALB/c nude mice were acquired from the National Laboratory Animal Center (Shanghai, China). Overall, 10 mice (n = 5 each group) were implanted with U251 cells stably knockdown circCDK14 by lentiviruses carrying sh-circCDK14 (Wanleibio, China), or control U251 cells with lentiviruses carrying sh-NC (Wanleibio, China). 5 x 10⁶ cells were resuspended in phosphatebuffered saline (100 ul) and Matrigel substrate (100 ul) and injected into the right flank of nude mice. Tumor volume was documented once 7 days after implantation. Click to Show/Hide
Response Description	CircCDK14 promotes the migration, invasion and proliferation of glioma cells in vitroas well as tumorigenesisin vivo. An evaluation of the underlying mechanism revealed that circCDK14 sponged miR-3938 to upregulate oncogenic gene PDGFRA expression. After knockdown of circCDK14 in glioma cells, protein levels of SLC7A11 and GPX4 decreased significantly and Fp became more sensitivity.

Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1)

Regulator Info

Pancreatic cancer [ICD-11: 2C10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[57]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
Response Description	PTPMT1 is upregulated in pancreatic cancer and PTPMT1 inhibits ferroptosis by suppressing the expression of ACSL4 and upregulating SLC7A11 in Panc-1 cells, suggesting PTPMT1 might be a potential prognosis biomarker and therapeutic target in PDAC.

Peroxiredoxin-6 (PRDX6)

Regulator Info

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[42]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MPC-5 cells	Normal	Mus musculus	CVCL_AS87
In Vivo Model	Male C57BL/6 mice (6-8 weeks old, 20-25 g) were obtained from KCI BioTech (Jiangsu, China. Mice were intraperitoneally injected 50 mg/kg/day of STZ for 5 straight days to generate DN mouse. At 3 days post injection, glucose levels were measured from tail blood, and blood glucose level more than 16.4 mmol/L indicated that DN models was established. Click to Show/Hide
Response Description	Prdx6 overexpression also eliminated ferroptosis caused by HG, which was reflected in the suppression of iron accumulation and the increase in SLC7A11 and GPX4 expression. Moreover, Sp1 could bind to the three Sp1 response elements in the Prdx6 promoter, thereby directly regulating the transcriptional activation of Prdx6 in podocytes. Further, Prdx6 overexpression attenuated renal injuries in streptozotocin-induced diabetic nephropathy mice.

PCAT1 (IncRNA)

Regulator Info

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[45]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	22Rv1 cells	Prostate carcinoma	Homo sapiens	CVCL_1045
In Vivo Model	PC3 and PC3/DR cells (5 x 10⁶ cells) were subcutaneously injected into each flank of six-week-old male BALB/c nude mice (HFK Biotech, China). When the tumor volume reached 100 mm³, the mice were treated with Dimethyl Sulfoxide (DMSO) alone, DTX (5 mg/kg body weight, every two days) with DMSO or erastin (20 mg/kg body weight in 20 ul DMSO plus 130 ul corn oil, daily) by intraperitoneal injection. Click to Show/Hide
Response Description	DTX-resistant prostate cancer cells develop tolerance toward ferroptosis and that lncRNA PCAT1 promotes chemoresistance by blocking DTX-induced ferroptosis. Mechanistic studies indicated that PCAT1 activates the expression of SLC7A11 by interacting with c-Myc and sponging with miR-25-3p. In addition, TFAP2C activates PCAT1 expression to reduce ferroptosis susceptibility and enhance chemoresistance.

Pannexin-1 (PANX1)

Regulator Info

Preeclampsia [ICD-11: JA24]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[46]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hPTs (Human placental tissues)
Response Description	Panx1 and TLR4 are suggested to induce ferroptosis in Preeclampsia via SLC7A11-mediated signaling pathways, offering a novel perspective on PE pathogenesis and novel diagnostic tools for Preeclampsia.

OIP5-AS1 (IncRNA)

Regulator Info

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[58]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell invasion
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145 cells	Prostate carcinoma	Homo sapiens	CVCL_0105
In Vivo Model	A total of 2 x 10⁶ PC3 and PC3/Cd cells were subcutaneously injected into the right flanks of 4-week-old male Balb/c nude mice. Tumor burdens were closely monitored by tumor volumes. When the largest tumors reached a size of 1.0 cm3, all mice were sacrificed due to ethical considerations. Moreover, the final tumor weight was also recorded. Click to Show/Hide
Response Description	OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, lncRNA OIP5-AS1 promotes prostate cancer progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling.

Nuclear receptor subfamily 1 group D member 2 (NR1D2)

Regulator Info

Acute kidney failure [ICD-11: GB60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[59]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MRTEpiC (Mouse renal tubular epithelial cells)
	mRTECs (Mouse renal tubular epithelial cells)
	M4100-57 (Mouse renal tubular epithelial cells)
In Vivo Model	Gene knockout (Rev-erb-a-/-,Rev-erb-b-/-and icDKO) mice and wild-type littermates were treated with folic acid (i.p., 100 mg/kg, once daily for seven consecutive days) at ZT6 or ZT18 to induce acute kidney injury. Click to Show/Hide
Response Description	Rev-erb-b (NR1D2) promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. Targeted inhibition of Rev-erb-b limits ferroptosis to ameliorate folic acid-induced acute kidney injury in mice.

Nuclear receptor subfamily 1 group D member 1 (NR1D1)

Regulator Info

Acute kidney failure [ICD-11: GB60]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[59]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MRTEpiC (Mouse renal tubular epithelial cells)
	mRTECs (Mouse renal tubular epithelial cells)
	M4100-57 (Mouse renal tubular epithelial cells)
In Vivo Model	Gene knockout (Rev-erb-a-/-,Rev-erb-b-/-and icDKO) mice and wild-type littermates were treated with folic acid (i.p., 100 mg/kg, once daily for seven consecutive days) at ZT6 or ZT18 to induce acute kidney injury. Click to Show/Hide
Response Description	Rev-erb-a (NR1D1) promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. Targeted inhibition of Rev-erb-a limits ferroptosis to ameliorate folic acid-induced acute kidney injury in mice.

Neurogenic locus notch homolog protein 2 (NOTCH2)

Regulator Info

Hemangioma [ICD-11: 2E81]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[60]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
	Notch signaling pathway	hsa04330
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	hHemECs (Human hemangioma endothelial cells)
Response Description	Knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/ NOTCH2 axis. Importantly, silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2.

N6-adenosine-methyltransferase non-catalytic subunit (METTL14)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[61]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Glutamate metabolism			hsa00250
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	SMMC-7721 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
	MHCC97-H cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	PLC/PRF/5 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0485
	BEL-7402 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In Vivo Model	The BALB/C nude mice were obtained from Shanghai SLAC Laboratory Animal Co., Ltd. 5 x 10⁵ stable SLC7A11-knockdown HCCLM3 cells or SLC7A11-vector cells were injected subcutaneously into BALB/C nude mice. After 5 weeks, mice were killed, and tumour photograph was detected with photography. In the other animal work, 5 x 10⁵ stable METTL14-vector HCCLM3 cells, SLC7A11-Overexpression cells or SLC7A11-R298P cells were injected subcutaneously into BALB/C nude mice. Click to Show/Hide
Response Description	METTL14 induced m6A modification at 5'UTR of SLC7A11 mRNA, which in turn underwent degradation relied on the YTHDF2-dependent pathway. Importantly, ectopic expression of SLC7A11 strongly blocked METTL14-induced tumour-suppressive effect in hypoxic hepatocellular carcinoma.

Myc proto-oncogene protein (MYC)

Regulator Info

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[45]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	22Rv1 cells	Prostate carcinoma	Homo sapiens	CVCL_1045
In Vivo Model	PC3 and PC3/DR cells (5 x 10⁶ cells) were subcutaneously injected into each flank of six-week-old male BALB/c nude mice (HFK Biotech, China). When the tumor volume reached 100 mm³, the mice were treated with Dimethyl Sulfoxide (DMSO) alone, DTX (5 mg/kg body weight, every two days) with DMSO or erastin (20 mg/kg body weight in 20 ul DMSO plus 130 ul corn oil, daily) by intraperitoneal injection. Click to Show/Hide
Response Description	Docetaxel (DTX)-resistant prostate cancer cells develop tolerance toward ferroptosis and that lncRNAPCAT1 promotes chemoresistance by blocking DTX-induced ferroptosis. Mechanistic studies indicated that PCAT1 activates the expression of SLC7A11 by interacting with c-Myc and sponging with miR-25-3p. In addition, TFAP2C activates PCAT1 expression to reduce ferroptosis susceptibility and enhance chemoresistance.

Mucin-1 (MUC1)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[62]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MDA-MB-468 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
Response Description	MUC1-C binds directly with CD44v and in turn promotes stability of xCT (SLC7A11) in the cell membrane in breast adenocarcinoma. The interaction between 2MUC1-C and xCT is further supported by the demonstration that targeting xCT with silencing or the inhibitor sulfasalazine suppresses MUC1 gene transcription by increasing histone and DNA methylation on the MUC1 promoter.

mmu-miR-378a-3p (miRNA)

Regulator Info

Kidney injury [ICD-11: NB92]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[63]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
	TCMK-1 cells	Normal	Mus musculus	CVCL_2772
In Vivo Model	Male Sprague-Dawley (SD) rats (5 weeks old, weighting 180-220 g) were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. SD rats were anesthetized with an intraperitoneal (i.p.) injection of pentobarbital sodium (25 mg/kg) and placed on a surgical thermostator. Then the rats were subjected to an abdominal incision, and the right kidney was carefully liberated from surrounding tissue, and nephrectomy was performed. The left kidney was exposed after a midline incision, and the renal artery was clamped with non-traumatic clamps for 45 min, followed by restoring of the renal blood flow. The kidneys were harvested and the serum was collected 48 h after the surgery. The rats in sham group were subjected to an abdominal incision without clamping the renal artery. Click to Show/Hide
Response Description	MiR-182-5p and miR-378a-3p induced ferroptosis in cells. And miR-182-5p and miR-378a-3p regulated the expression of GPX4 and SLC7A11 negatively by directly binding to the 3'UTR of GPX4 and SLC7A11 mRNA. In vivo study showed that silencing miR-182-5p and miR-378a-3p alleviated the I/R-induced kidney injury in rats.

MIT domain-containing protein 1 (MITD1)

Regulator Info

Hereditary Leiomyomatosis [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[64]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Hippo signaling pathway			hsa04390
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
	786-O cells	Renal cell carcinoma	Homo sapiens	CVCL_1051
	ACHN cells	Papillary renal cell carcinoma	Homo sapiens	CVCL_1067
	A-498 cells	Renal cell carcinoma	Homo sapiens	CVCL_1056
	769-P cells	Renal cell carcinom	Homo sapiens	CVCL_1050
	Caki-1 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
Response Description	MITD1 knockdown inhibited clear cell renal cell carcinoma (ccRCC) cell proliferation and migration and induced ferroptosis in ccRCC. Subsequent overexpression experiments demonstrated that MITD1 knockdown induced ferroptosis and suppressed tumor growth and migration through the TAZ/SLC7A11 pathway.

Membrane-associated progesterone receptor component 1 (PGRMC1)

Regulator Info

Head neck squamous cell carcinoma [ICD-11: 2D60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[65]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	NH-3 cells	Tongue squamous cell carcinoma	Homo sapiens	CVCL_8126
	HN4 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_IS30
In Vivo Model	Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from OrientBio (Seoul, Republic of Korea). HN4 cells with transfection of PGRMC1 overexpression or control vector and HN4PCC with shPGRMC1 or control vector were subcutaneously injected into the bilateral flank of nude mice. When gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route). Click to Show/Hide
Response Description	GRMC1-dependent lipophagy promotes ferroptosis in paclitaxel-tolerant persister cancer cells. PGRMC1 expression increased FAO and ferroptosis sensitivity from in vivo mice experiments. And PGRMC1 promotes ferroptosis by xCT (SLC7A11) inhibition in head and neck cancer (HNC) cells.

MEG8 (IncRNA)

Regulator Info

Hemangioma [ICD-11: 2E81]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[60]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
	Notch signaling pathway	hsa04330
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	hHemECs (Human hemangioma endothelial cells)
Response Description	Knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis. Importantly, silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2.

Lysine-specific demethylase 4A (KDM4A)

Regulator Info

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[66]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell metastasis
In Vitro Model	143B cells	Osteosarcoma	Homo sapiens	CVCL_2270
	HOS cells	Osteosarcoma	Homo sapiens	CVCL_0312
In Vivo Model	For the xenograft mouse model, 1 x 10⁶ OS 143B cells in 100 uL PBS were subcutaneously injected with 1 x 10⁶ OS cells. For the OS lung metastasis model and in vivo imaging, 1 x 10⁶ 143B cells in 10 uL PBS were injected orthotopically into the medullary cavity of the tibia of mice. For bioluminescent imaging, we used 143B cells stably expressing luciferase, and the luciferase substrate D-Luciferin (Selleck, China) was retro-orbitally injected before imaging on days 7 and 21. Click to Show/Hide
Response Description	KDM4A regulates SLC7A11 transcription and osteosarcoma cell ferroptosis by controlling H3K9me3 demethylation in the promoter region of SLC7A11. The findings suggestes that KDM4A activity may be a potential therapeutic target for future OS treatment.

Lysine-specific demethylase 3B (KDM3B)

Regulator Info

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[67]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	HEK293 cells	Normal	Homo sapiens	CVCL_0045
	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
Response Description	Since KDM3B has been shown to associate with acute myeloid leukemia (AML). KDM3B protects cells from Erastininduced ferroptosis through transcriptional upregulation of SLC7A11 via interaction with ATF4.

LIM and SH3 domain protein 1 (LASP1)

Regulator Info

Thyroid cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[68]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	Nthy-ori3-1 cells	Normal	Homo sapiens	CVCL_2659
	IHH-4 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2960
	BCPAP cells	Thyroid carcinoma	Homo sapiens	CVCL_0153
	KTC-1 cells	Thyroid carcinoma	Homo sapiens	CVCL_6300
	TPC-1 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
In Vivo Model	Animal experiments were approved by ethics committee of Wuzhou Red Cross Hospital. The TPC-1 cells transfected with sh-CERS6-AS1 or sh-NC were made into cell suspension (2 x 10⁶/ml) with PBS. Then nude mice were randomly divided into sh-CERS6-AS1 group (n = 6) and sh-NC group (n = 6). The mice were subcutaneously inoculated with 200 ul corresponding cell suspension respectively, and then the weight and tumor volume of mice were recorded every other week. After 5 weeks, pentobarbital sodium (120 mg/kg) were intraperitoneally injected to make nude mice euthanasia, and then the tumors were stripped and weighed. Subsequently, immunohistochemistry and RT-PCR were performed. Click to Show/Hide
Response Description	Silencing CERS6-AS1 suppressed cell viability and increased ferroptosis in papillary thyroid cancer. LASP1 was modulated by CERS6-AS1 through sponging miR-497-5p. The expression of Ki67, PCNA, GPX4, and SLC7A11 was inhibited by si-CERS6-AS1 transfection.

Kelch domain-containing protein 3

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[69]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell growth
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	SJSA-1 cells	Osteosarcoma	Homo sapiens	CVCL_1697
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	HCCLM3 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In Vivo Model	4-6-week-old female BALB/c nu/nu mice obtained from SLAC Laboratory Animal Co., Ltd. were bred and maintained in our institutional pathogen-free mouse facilities. Ovarian tumors were established by subcutaneously injecting 5 x 10⁶ SKOV3 cells in 100 ul of PBS buffer into the right flank of 6-week-old nude mice (four mice for each group). At the end of 3 weeks, mice were killed and in vivo solid tumors were dissected and weighed. Click to Show/Hide
Response Description	KLHDC3 expression is elevated in ovarian cancer. KLHDC3 suppresses ferroptosis in vitro and supports tumor growth in vivo by relieving p14ARF-mediated suppression of SLC7A11 transcription.

Interleukin-6 (IL6)

Regulator Info

Head neck squamous cell carcinoma [ICD-11: 2D60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[51]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ferroptosis			hsa04216
	JAK-STAT signaling pathway			hsa04630
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HN4 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_IS30
	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
In Vivo Model	Four-week-old male BALB/c-nu mice were purchased from the Shanghai Laboratory Animal Center (Shanghai, China). About 4 x 10⁶ CAL27 cells were stably transfected with lentivirus. After administration of 2 ug/mL puromycin for three days, transfection efficiency was confirmed by western blotting. Approximately 2 x 10⁶ transfected cells were subcutaneously injected into flanks. For the drug-administration study, 20 mg/kg erastin (S7242, Selleck Chemicals) were administrated intraperitoneally twice every other day. Approximately 20 uL IL-6 (10 ug/mL, PeproTech, USA) were given intratumorally twice every other day. Click to Show/Hide
Response Description	The study demonstrate the critical role of IL-6-induced ferroptosis resistance during head and neck squamous cell carcinoma carcinogenesis. The IL-6/STAT3/xCT (encoded by SLC7A11) axis acts as a novel mechanism driving tumor progression and thus may potentially be utilized as a target for tumor prevention and therapy.

Interferon gamma (IFNG)

Regulator Info

Fibrosarcoma [ICD-11: 2B53]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[70]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	A-375 cells	Amelanotic melanoma	Homo sapiens	CVCL_0132
	B16-F0 cells	Melanoma	Mus musculus	CVCL_0604
	ID8 cells	Ovarian cancer	Mus musculus	CVCL_IU14
In Vivo Model	Six- to eight-week-old female NSG or C57BL/6 mice were obtained from the Jackson Laboratory. For HT-1080 tumor model, 10⁶ tumor cells were subcutaneously injected on the right flank of NSG mice. For adoptive transfer of OT-I to B16-OVA model, 105 B16-OVA cells were subcutaneously injected on the right flank of C57BL/6 mice. For the B16 tumor model, 105 B16F0 cells were subcutaneously injected on the right flank of C57BL/6 mice. For the ID8 tumor model, 2 x 10⁶ luciferase-expressing ID8 cells were injected into the peritoneal cavity of each female mouse. Click to Show/Hide
Response Description	Interferon gamma (IFNG) released from CD8T cells downregulates the expression of SLC3A2 and SLC7A11, two subunits of the glutamate-cystine antiporter system xc-, impairs the uptake of cystine by tumour cells, and as a consequence, promotes tumour cell lipid peroxidation and ferroptosis in Fibrosarcoma.

hsa-miR-770-5p (miRNA)

Regulator Info

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[44]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mKTs (Mouse knee tissues)
	HK-2 (Human renal glomerular endothelial cells)
In Vivo Model	All C57BL/6 mice (5-6 weeks, 18-20 g) were obtained from Animal Testing Center of Qinglongshan (Nanjing, Suzhou, China). DN mice were fed with a high-fat diet (HFD) for 12 weeks and then injected with STZ (30 mg/kg of streptozotocin; Sigma-Aldrich, St Louis, MO, USA) i.p. for 7 consecutive days. Blood glucose levels of mice were measured using 16.7 mmol/l after one week of the final injection. Then, mice were killed under anesthesia and their kidneys taken for analysis after induction of STZ at 4 months. Click to Show/Hide
Response Description	Circular RNA circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/ SLC7A11 by miR-770-5p. Importantly, this research indicated that circ ASAP2 might act as a target for improving the role of ferroptosis in diabetes nephropathy.

hsa-miR-587 (miRNA)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[71]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	ES-2 cells	Ovarian clear cell adenocarcinoma	Homo sapiens	CVCL_3509
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	Caov-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0201
Response Description	ADAMTS9-AS1 regulated SLC7A11 expression through miR-587, thereby affecting ferroptosis, proliferation and migration of Epithelial ovarian cancer cells.

hsa-miR-545-3p (miRNA)

Regulator Info

Thyroid cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[72]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	FTC-133 cells	Thyroid gland follicular carcinoma	Homo sapiens	CVCL_1219
	TPC-1 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
In Vivo Model	BALB/c nude mice (18-20 g, 4-week-old, male) (n = 6) were purchased and applied for the tumor growth analysis of FTC133 cellsin vivo. About 1 x 10⁶ FTC133 cells were transfected with control shRNA or circ_0067934 shRNA and were subcutaneously injected into the left fat pad of mice. After 5 days of injection, we measured tumor growth every 5 days. We sacrificed the mice after 30 days of injection. The tumor volume was calculated by (length x width2)/2. And the tumor weight was calculated at day 30. Click to Show/Hide
Response Description	Circ_0067934 upregulated the expression of the ferroptosis-negative regulator SLC7A11 by sponging and inhibiting miR-545-3p in thyroid cancer cells. The overexpression of SLC7A11 or the inhibitor of miR-545-3p reversed circ_0067934 silencing-regulated thyroid cancer cell proliferation.

hsa-miR-520d-5p (miRNA)

Regulator Info

Oral squamous cell carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[73]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
	SCC-15 cells	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
In Vivo Model	The tumorigenicity analysis was conducted in BALB/c nude mice (6-weeks-old, male). The mice were maintained at pathogen-free condition. The 5 x 10⁶ CAL27 cells were treated with control shRNA or circFNDC3B shRNA and subcutaneously injected into the nude mice (N = 5). The mice were sacrificed after 30 days and the tumor volume was calculated using the formula of (length x width2)/2. Click to Show/Hide
Response Description	CircFNDC3B attenuated ferroptosis of Oral squamous cell carcinoma (OSCC) cells and contributed to OSCC progression by regulating the miR-520d-5p/SLC7A11 axis. CircFNDC3B, miR-520d-5p, and SLC7A11 may serve as potential therapeutic targets of OSCC.

hsa-miR-520a-5p (miRNA)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[74]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
In Vivo Model	SCID/nude mice (6 weeks old) were ordered from Laboratory Animal Center of Chinese Academy of Sciences (Beijing, China). HT29 cells were co-transfected with sh-circFOXP1 and pCMV-SLC7A11 or empty vector. Cells were digested, 5 x 10⁶ cells were mixed with Matrigel (Corning) and subcutaneously injected into mice. The width and length of tumor were measured at indicated time, and the tumor size was calculated by the formula: 0.5 x length x width2. Mice were then succumbed to death, the tumors were isolated, weighted, and made into paraffin-embedded slices (5-um). The slices were stained with anti-KI67 antibody (Santa Cruz Biotechnology) and subsequent HRP-labeled secondary antibody and captured in a microscope (Leica Microsystems). Click to Show/Hide
Response Description	Mechanically, circFOXP1 increased SLC7A11 expression by directly sponging miR-520a-5p in lung cancer cells. The inhibitor of miR-520a-5p or the overexpression of SLC7A11 reversed circFOXP1 shRNA-induced ferroptosis phenotypes in lung cancer cells.

hsa-miR-515-5p (miRNA)

Regulator Info

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[75]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Ca Ski cells	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	hCECs (Human cervical epithelial cells)
In Vivo Model	The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 10⁷ cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured. Click to Show/Hide
Response Description	CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/409-3P/ 515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis.

Ovarian dysfunction [ICD-11: 5A80]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[76]
Regulator for Ferroptosis	Driver
Pathway Response	Glutathione metabolism			hsa00480
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	KGN cells	Ovarian granulosa cell tumor	Homo sapiens	CVCL_0375
	SVOG-3e cells	Normal	Homo sapiens	CVCL_IN98
In Vivo Model	We recruited 12 infertility patients (6 PCOS and 6 controls) aged 20 and 38 who underwent in vitro fertilization (IVF) at the Department of Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-Sen University. All patients were treated the antagonist stimulation protocol. Briefly, on cycle day 2, ovarian stimulation was started by daily injection of recombinant FSH (r-FSH) (Gonal-F; Merck Serono). Gonadotropin-releasing hormone (GnRH) antagonist (Cetrotide, 0.25 mg; Merck Serono) injection was started from the day 6 of stimulation. When at least three follicles had reached 17 mm or two follicles had reached 18 mm in diameter, an intramuscular injection of 5,000 IU-10000 IU of human chorionic gonadotropin (hCG) is used for triggering final oocyte maturation. Click to Show/Hide
Response Description	circRHBG inhibits ferroptosis in Polycystic ovary syndrome cells through the circRHBG/ miR-515-5p/SLC7A11 axis in PCOS, which may provide new diagnostic molecular markers and therapeutic targets for PCOS.

hsa-miR-513a-3p (miRNA)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[77]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	hESCCs (Esophageal squamous cancer cells)
Response Description	Downregulation of BBOX1-AS1 inhibits cell proliferation, and metastasis accelerates cell apoptosis and ferroptosis in esophageal squamous cell cancer by upregulating miR-513a-3p to reduce SLC7A11 expression. These findings may provide novel insights into the diagnosis and treatment of ESCC.

hsa-miR-5096 (miRNA)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[78]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MDA-MB-468 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	MDA-MB-453 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0418
	BT-549 cells	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	SK-BR-3 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	ZR-75-1 cells	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	MCF-10A cells	Normal	Homo sapiens	CVCL_0598
In Vivo Model	Mating was setup 2 days prior to injection day and zebrafish embryos were collected and incubated in E3 embryo medium (5 mM NaCl, 0.17 mM KCl, 10 mM HEPES, 0.33 mM MgSO4·7H2O, 0.33 mM CaCl2·6H2O, and 0.00001% methylene blue) containing 0.2 mM N-phenyl-thiourea (PTU) (catalog no: P7629, Sigma-Aldrich). Two days post-fertilization, the chorion was removed manually using fine forceps, and the embryos were anesthetized using E3 medium containing 200 mg/L Ethyl 3-aminobenzoate methanesulfonate (Tricaine) (catalog no: A5040, Sigma-Aldrich). Anesthetized embryos were mounted in 0.7% low melting agarose containing 200 ug/ml of Tricaine and were microinjected with 500 cells in the yolk sac using Nanoject III (catalog no: 3-000-207; Drummond Scientific Company, PA, USA). At 1 day post-injection (dpi), embryos with similar graft size were selected and imaged using both bright field and RFP channels and incubated in E3-PTU medium containing 5 ug/ml doxycycline at 34 until further imaging. At 4 dpi, embryos were anesthetized and imaged again using both bright field and RFP channels using Olympus IX-73 microscope. Cells that migrated outside the yolk sac (injection site) were represented by a notable fluorescent dot and considered a metastatic event; these were counted manually for all embryos in each experimental group. Click to Show/Hide
Response Description	The present study demonstrated that miR-5096 targets and downregulates SLC7A11, thereby providing a mechanistic basis for ferroptosis in human breast cancer cells. In addition, miR-5096 induced cell death via ferroptosis, characterized by mitochondrial shrinkage with partial loss of cristae with simultaneous changes in ACSL4, ROS, lipid ROS, OH-, reactive iron, GSH, and MMP levels.

hsa-miR-497-5p (miRNA)

Regulator Info

Thyroid cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[68]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	Nthy-ori3-1 cells	Normal	Homo sapiens	CVCL_2659
	IHH-4 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2960
	BCPAP cells	Thyroid carcinoma	Homo sapiens	CVCL_0153
	KTC-1 cells	Thyroid carcinoma	Homo sapiens	CVCL_6300
	TPC-1 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
In Vivo Model	Animal experiments were approved by ethics committee of Wuzhou Red Cross Hospital. The TPC-1 cells transfected with sh-CERS6-AS1 or sh-NC were made into cell suspension (2 x 10⁶/ml) with PBS. Then nude mice were randomly divided into sh-CERS6-AS1 group (n = 6) and sh-NC group (n = 6). The mice were subcutaneously inoculated with 200 ul corresponding cell suspension respectively, and then the weight and tumor volume of mice were recorded every other week. After 5 weeks, pentobarbital sodium (120 mg/kg) were intraperitoneally injected to make nude mice euthanasia, and then the tumors were stripped and weighed. Subsequently, immunohistochemistry and RT-PCR were performed. Click to Show/Hide
Response Description	Silencing CERS6-AS1 suppressed cell viability and increased ferroptosis in papillary thyroid cancer. LASP1 was modulated by CERS6-AS1 through sponging miR-497-5p. The expression of Ki67, PCNA, GPX4, and SLC7A11 was inhibited by si-CERS6-AS1 transfection.

Hemangioma [ICD-11: 2E81]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[60]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
	Notch signaling pathway	hsa04330
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	hHemECs (Human hemangioma endothelial cells)
Response Description	Knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis. Importantly, silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2.

hsa-miR-409-3p (miRNA)

Regulator Info

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[75]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Ca Ski cells	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	hCECs (Human cervical epithelial cells)
In Vivo Model	The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 10⁷ cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured. Click to Show/Hide
Response Description	CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/ 409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis.

hsa-miR-3938 (miRNA)

Regulator Info

Glioblastoma [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[56]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	HEB (Human glial cells)
	SF126 cells	Glioblastoma	Homo sapiens	CVCL_1688
	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
In Vivo Model	4-week-old female BALB/c nude mice were acquired from the National Laboratory Animal Center (Shanghai, China). Overall, 10 mice (n = 5 each group) were implanted with U251 cells stably knockdown circCDK14 by lentiviruses carrying sh-circCDK14 (Wanleibio, China), or control U251 cells with lentiviruses carrying sh-NC (Wanleibio, China). 5 x 10⁶ cells were resuspended in phosphatebuffered saline (100 ul) and Matrigel substrate (100 ul) and injected into the right flank of nude mice. Tumor volume was documented once 7 days after implantation. Click to Show/Hide
Response Description	CircCDK14 promotes the migration, invasion and proliferation of glioma cells in vitroas well as tumorigenesisin vivo. An evaluation of the underlying mechanism revealed that circCDK14 sponged miR-3938 to upregulate oncogenic gene PDGFRA expression. After knockdown of circCDK14 in glioma cells, protein levels of SLC7A11 and GPX4 decreased significantly and Fp became more sensitivity.

hsa-miR-378a-3p (miRNA)

Regulator Info

Nerve injury [ICD-11: NA04]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[79]
Regulator for Ferroptosis	Driver
Pathway Response	Glutathione metabolism			hsa00480
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	All the animals were housed in a temperature- and humidity-controlled room under a 12 h light/dark cycle and maintained in standard cages with free access to food and water. After seven days of breeding, the mice were randomly assigned to four groups of fifteen animals each. The animals in the four groups were treated with Pb acetate indrinking waterat doses of 0, 250 mg/L, 500 mg/L, and 1000 mg/L (control, LPb, MPb, and HPb groups, respectively). The Pb exposure period was 12 weeks. Click to Show/Hide
Response Description	Inhibition of miR-378a-3p expression reversed the reduction in GSH and the increase in lipid ROS levels induced by lead exposure. MiR-378a-3p exerted an important effect by regulating SLC7A11 expression in nerve injury induced by lead exposure.

hsa-miR-375-3p (miRNA)

Regulator Info

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[80]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell stemness
In Vitro Model	SGC-7901 cells	Gastric carcinoma	Homo sapiens	CVCL_0520
	BGC-823 cells	Gastric carcinoma	Homo sapiens	CVCL_3360
	GES-1 cells	Normal	Homo sapiens	CVCL_EQ22
In Vivo Model	Four- to eight-week-old female BALB/c nude mice were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). For the tumor-limiting dilution assay, 1 x 10⁷, 5 x 10⁶, and 2.5 x 10⁶ of LV3-miR-375 cells, LV3-SLC7A11 cells, LV3-shSLC7A11 cells, LV3-miR-375-SLC7A11 cells, and LV3-NC cells (BGC-823 and SGC-7901) were subcutaneously implanted into the underarm of mice. Fifteen days later, all mice were euthanized and tumor tissues were collected and weighed. For metastasis experiment, mouse models were established by intravenous injection of cells. Three mice per group were injected with 2 x 10⁶ cells in 200 uL RPMI-1640 serum-free media. Six weeks after injection, mice were sacrificed for collecting lung tissues. Click to Show/Hide
Response Description	MiR-375 reduced the stemness of gastric cancer cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis.

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[75]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Ca Ski cells	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	hCECs (Human cervical epithelial cells)
In Vivo Model	The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 10⁷ cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured. Click to Show/Hide
Response Description	CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1- miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis.

hsa-miR-372-3p (miRNA)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[82]
Regulator for Ferroptosis	Suppressor
Pathway Response	Glutathione metabolism			hsa00480
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	TE-1 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	Eca-109 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	HET-1A cells	Normal	Homo sapiens	CVCL_3702
Response Description	ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11.

hsa-miR-367-3p (miRNA)

Regulator Info

Multiple sclerosis [ICD-11: 8A40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[83]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBMSCs (Bone marrow stromal cells)
	BV-2 cells	Normal	Mus musculus	CVCL_0182
In Vivo Model	Female C57BL6 mice were randomized into four groups (n = 8/group): the control group (non-EAE mice), the EAE group (EAE mice injected intrathecally with 5 uL PBS when symptoms appeared), the EAE + BMSCs-Exo + mimic negative control (NC) group (EAE mice injected intrathecally with Exos from bone MSCs (BMSCs) transfected with mimic NC [5 uL, 2 ug/L in PBS] when symptoms appeared), and the EAE + BMSCs-Exo + miR-367-3p mimic group (EAE mice injected intrathecally with Exos from BMSCs transfected with miR-367-3p mimic [5 uL, 2 ug/L in PBS] when symptoms appeared). Click to Show/Hide
Response Description	MiR-367-3p can be delivered by BMSC-Exos into microglia, where miR-367-3p inhibits EZH2 expression and activates the expression of SLC7A11, suppressing microglial ferroptosis and relieving the symptoms of EAE. Experimental autoimmune encephalomyelitis (EAE) is a typical animal model of multiple sclerosis.

hsa-miR-34c-3p (miRNA)

Regulator Info

Oral squamous cell carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[84]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	SCC-25 cells	Squamous carcinoma	Homo sapiens	CVCL_1682
	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
	HOK cells	Normal	Hexagrammos otakii	CVCL_YE19
Response Description	Low expression of miR-34c-3p in oral squamous cell carcinoma, negatively regulating SLC7A11 expression, promoting ferroptosis, and suppressing cell proliferation.

hsa-miR-339-3p (miRNA)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[35]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis			hsa04216
	Glutathione metabolism			hsa00480
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell metastasis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	16HBE14o- cells	Normal	Homo sapiens	CVCL_0112
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In Vivo Model	6-8 weeks mice were divided into 4 groups randomly. Mice were injected with 2.5 x 10⁵ wild type LLC cells, Uc.339 OE-LLC cells, with or without miR-339 inhibitors, respectively, through the lateral tail vain. The mice were killed after 4 weeks by carbon dioxide asphyxiation followed by cervical dislocation to ensure death. The lungs were removed, rinsed with PBS, and the number of metastatic foci on the lung surface was counted. The pulmonary lobes were subsequently kept in 4% paraformaldehyde for later paraffin embedding and hematoxylin and eosin staining. Click to Show/Hide
Response Description	LncRNA Uc.339 competitively binds to pri-miR-339 and inhibits the production of mature miR-339. At the same time, it is the first to clarify the reason for the negative correlation between miR-339 and SLC7A11 expression in lung cancer, and for the first verification that the inhibition of miR-339 led to increased expression of SLC7A11 and weakens ferroptosis, which constituted an important carcinogenesis mechanism for lung adenocarcinoma metastasis.

hsa-miR-30b-5p (miRNA)

Regulator Info

Preeclampsia [ICD-11: JA24]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[85]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HTR-8/SVneo cells	Normal	Homo sapiens	CVCL_7162
	hETCs (Human first-trimester extravillous trophoblast cells)
In Vivo Model	Pregnant SD rats were randomly dived into four groups: sham group (n = 8), PE group (n = 8), PE + ferrostatin-1 group ( n= 8), and PE + miR-30b-5p inhibition group (n = 8). On day 14 of pregnancy, PE rat model was established through reduced uterine perfusion pressure (RUPP) surgery, wherein constrictive silver clips were placed on the aorta (0.203-mm clips) superior to the iliac bifurcation and on the ovarian vessels (0.100-mm clips), according to a previous description. Sham rats were operated on in a fashion similar to that of RUPP rats, but without clipping. Mini-pumps were also intraperitoneally inserted into rats on day 14 of pregnancy. The mini-pump in each rat delivered the ferrostatin-1 at a dose of 10 umol/kg/day for 5 days. An miR-30b-5p antagonist (GenePharma) was injected from the tail veins on day 13 of gestation, at a rate of 100 uL/day for 6 days. The blood pressure was measured on days 14, 16, and 19 of gestation using catheters inserted into the carotid artery and jugular vein. Click to Show/Hide
Response Description	Abnormally up-regulated miR-30b-5p triggered the ferroptosis in trophoblasts under hypoxic conditions by down-regulating SLC7A11, Pax3, and Pax3-downstream target, FPN1. Blockage of miR-30b-5p up-regulation or direct inhibition of ferroptosis attenuated preeclampsia (PE) symptoms in the rat model, making miR-30b-5p a potential therapeutic target for preeclampsia.

hsa-miR-30a-5p (miRNA)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[86]
Regulator for Ferroptosis	Driver
Pathway Response	Wnt signaling pathway			hsa04310
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell invasion
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	KYSE-70 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1356
	hEECs (Human esophageal epithelial cells)
In Vivo Model	BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 10⁶) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. Click to Show/Hide
Response Description	CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathways via miR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11.

hsa-miR-27a-3p (miRNA)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[87]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Description	MiR-27a-3p, was an essential modulator of ferroptosisviadirectly targeting SLC7A11 in non-small cell lung cancer cells. Overexpressing miR-27a-3p led to SLC7A11 suppressionviadirectly binding to its 3'-UTR, followed by the reduction of erastin-caused ferroptosis.

Ischemia/reperfusion injury [ICD-11: DB98]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[88]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis	hsa04216
	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	The rats were anesthetized by intraperitoneal injection of pentobarbital sodium (40 mg/kg). Before the experiment, the rats were fasted for 8-10 h and ensured sufficient water. The left common carotid artery (CCA) and left external carotid artery (ECA) were ligated after skin incision in the middle of the neck. In the common carotid artery cut a small incision. In order to induce ischemia, a cord plug was inserted through the incision into the internal carotid artery (ICA) and then to the origin of the middle cerebral artery (MCA). After ischemia for 2 h, the rats were anesthetized and gently pulled out the cord plug. At the end of the reperfusion time, the rats were euthanized by injection of a minimal lethal dose of anesthesia. Click to Show/Hide
Response Description	The results of dual luciferase reporter gene technique indicated SLC7A11 as the target gene of miR-27a. In the current study, miR-27a upregulates ferroptosis to aggravate cerebral ischemia-reperfusion injury by SLC7A11.

hsa-mir-27a (Precursor RNA)

Regulator Info

Cerebral ischemia [ICD-11: 8B10]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[89]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	The male Sprague Dawley rats were randomly divided into control group, sham group, middle cerebral artery occlusion/reperfusion model group (MCAO/R group) (according to different ischemia reperfusion time, the model group was divided into the 3, 6, 12 and 24 hours reperfusion groups after 2 hour-ischemia), and vehicle group, agomir-27a group, antagomir-27a group. The Zea-Longa method was used to establish rat MCAO model. Click to Show/Hide
Response Description	In the process of cerebral ischemia and reperfusion, the up-regulated miR-27a may induce ferroptosis through inhibiting SLC7A11, thus causing brain tissue damage.

hsa-miR-25-3p (miRNA)

Regulator Info

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[45]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	22Rv1 cells	Prostate carcinoma	Homo sapiens	CVCL_1045
In Vivo Model	PC3 and PC3/DR cells (5 x 10⁶ cells) were subcutaneously injected into each flank of six-week-old male BALB/c nude mice (HFK Biotech, China). When the tumor volume reached 100 mm³, the mice were treated with Dimethyl Sulfoxide (DMSO) alone, DTX (5 mg/kg body weight, every two days) with DMSO or erastin (20 mg/kg body weight in 20 ul DMSO plus 130 ul corn oil, daily) by intraperitoneal injection. Click to Show/Hide
Response Description	Docetaxel (DTX)-resistant prostate cancer cells develop tolerance toward ferroptosis and that lncRNAPCAT1 promotes chemoresistance by blocking DTX-induced ferroptosis. Mechanistic studies indicated that PCAT1 activates the expression of SLC7A11 by interacting with c-Myc and sponging with miR-25-3p. In addition, TFAP2C activates PCAT1 expression to reduce ferroptosis susceptibility and enhance chemoresistance.

hsa-miR-206 (miRNA)

Regulator Info

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[48]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	SJSA-1 cells	Osteosarcoma	Homo sapiens	CVCL_1697
Response Description	LncRNA SNHG14 targeted and down-regulated the expression of miR-206, further affecting the common ferroptosis inhibitor SLC7A11, and preventing NR-SJSA1 cells from undergoing ferroptosis. In conclusion, our findings highlight the involvement of lncRNA SNHG14 in ferroptosis and chemotherapy resistance of nutlin3a-resistant NR-SJSA1 cells, thus shedding new insight on how to overcome drug resistance in osteosarcoma cells and improve treatment efficacy.

hsa-miR-194-5p (miRNA)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[90]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In Vitro Model	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
Response Description	circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in ovarian cancer.

hsa-miR-143-3p (miRNA)

Regulator Info

Hereditary Leiomyomatosis [ICD-11: 2C90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[49]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
Response Description	SLC16A1-AS1 served as a sponge of miR-143-3p, and knockdown SLC16A1-AS1 significantly increased the enrichment of miR-143-3p. And then, SLC7A11 was identified as the target protein of miR-143-3p, and overexpression miR-143-3p remarkably inhibited the expression of SLC7A11. And silencing lncRNA SLC16A1-AS1 can induce ferroptosis through miR-143-3p/SLC7A11 signaling in renal cell carcinoma.

Ischemia/reperfusion injury [ICD-11: DB98]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[52]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	AC16 [Human hybrid cardiomyocyte] cells	Normal	Homo sapiens	CVCL_4U18
Response Description	SEMA5A-IT1 overexpression upregulated the expression of BCL2 and SLC7A11 through sponging miR-143-3p, thereby protecting cardiomyocytes against apoptotic and ferroptosis cell death. In conclusion, we propose that SEMA5A-IT1, which is transported to cardiomyocytes through circulating sEVs, is an important regulatory molecule that protects cardiomyocytes from ischemia-reperfusion injury.

hsa-miR-140-5p (miRNA)

Regulator Info

Myocardial injury [ICD-11: NB31]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[91]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Six-week-old C57BL/6 male mice were randomly divided into two groups; the first group was fed a 45% high fat diet for 20 weeks while the control group were fed a normal chow diet. ATM-exosomes isolated from obese and lean mice were transferred into normal mice via tailvein injection(30 ug per week), as previously described. To investigate glutathione synthesis, 20 mM l-buthionine-(S,R)-sulfoximine (BSO) was added to the drinking water and administered to mice for 2 weeks. To inhibit ferroptosis, mice were given an intraperitoneal injection with Fer-1 (1 mg/kg). Click to Show/Hide
Response Description	Solute carrier family 7 member 11 (SLC7A11) is a downstream target of miR-140-5p, which induces ferroptosis via inhibition of GSH synthesis by targeting SLC7A11. Attenuating exosomal-miR-140-5p expression alleviates ferroptosis and obesity-induced cardiac injury by alleviating GSH inhibition.

hsa-miR-128-3p (miRNA)

Regulator Info

Prostate cancer [ICD-11: 2C82]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[58]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell invasion
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145 cells	Prostate carcinoma	Homo sapiens	CVCL_0105
In Vivo Model	A total of 2 x 10⁶ PC3 and PC3/Cd cells were subcutaneously injected into the right flanks of 4-week-old male Balb/c nude mice. Tumor burdens were closely monitored by tumor volumes. When the largest tumors reached a size of 1.0 cm3, all mice were sacrificed due to ethical considerations. Moreover, the final tumor weight was also recorded. Click to Show/Hide
Response Description	OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, lncRNA OIP5-AS1 promotes prostate cancer progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling.

hsa-miR-1261 (miRNA)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[92]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell invasion
	Cell metastasis
In Vitro Model	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	BEL-7402 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	MHCC97-H cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
In Vivo Model	Four-week-old female BALB/c nude mice were subcutaneously inoculated with 2 x 10⁶ cells (5 mice per group). Intratumoral injection (40 uL of si-circ0097009 or negative control siRNA) was administered every 4 days. Mice were sacrificed, and tumor weights were measured after 4 weeks. To establish lung metastases, HepG2 cells were treated with 20 umol/L si-circ0097009. After 48 hours, cells (1 x 10⁵) were intravenously injected into the tail veins of mice (6 mice per group). Click to Show/Hide
Response Description	Circ0097009 acts as a competing endogenous RNA to regulate the expression of SLC7A11, a key regulator of cancer cell ferroptosis, by sponging miR-1261 in hepatocellular cancer. Circ0097009 may be used as a diagnostic biomarker for HCC and as a potential target for HCC therapy.

hsa-miR-125b-5p (miRNA)

Regulator Info

Oral squamous cell carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[93]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	Tca8113 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
	TSCCA cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_VL15
	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
	SCC-9 cells	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	hTECs (Human tongue epithelial cells)
Response Description	EZH2 inhibits the ferroptosis of tongue squamous cell carcinoma cells by inhibiting miR-125b-5p and enhancing SLC7A11. MiR-125b-5p regulates ferroptosis in TSCC cells by targeting SLC7A11.

Histone-lysine N-methyltransferase EZH2 (EZH2)

Regulator Info

Oral squamous cell carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[93]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	Tca8113 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
	TSCCA cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_VL15
	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
	SCC-9 cells	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1685
	hTECs (Human tongue epithelial cells)
Response Description	EZH2 inhibits the ferroptosis of tongue squamous cell carcinoma cells by inhibiting miR-125b-5p and enhancing SLC7A11. MiR-125b-5p regulates ferroptosis in TSCC cells by targeting SLC7A11.

Multiple sclerosis [ICD-11: 8A40]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[83]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBMSCs (Bone marrow stromal cells)
	BV-2 cells	Normal	Mus musculus	CVCL_0182
In Vivo Model	Female C57BL6 mice were randomized into four groups (n = 8/group): the control group (non-EAE mice), the EAE group (EAE mice injected intrathecally with 5 uL PBS when symptoms appeared), the EAE + BMSCs-Exo + mimic negative control (NC) group (EAE mice injected intrathecally with Exos from bone MSCs (BMSCs) transfected with mimic NC [5 uL, 2 ug/L in PBS] when symptoms appeared), and the EAE + BMSCs-Exo + miR-367-3p mimic group (EAE mice injected intrathecally with Exos from BMSCs transfected with miR-367-3p mimic [5 uL, 2 ug/L in PBS] when symptoms appeared). Click to Show/Hide
Response Description	MiR-367-3p can be delivered by BMSC-Exos into microglia, where miR-367-3p inhibits EZH2 expression and activates the expression of SLC7A11, suppressing microglial ferroptosis and relieving the symptoms of EAE. Experimental autoimmune encephalomyelitis (EAE) is a typical animal model of multiple sclerosis.

Hepatoblastoma [ICD-11: DB91]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[94]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hLCs (Liver cells)
	mPHs (Mouse primary hepatocytes)
In Vivo Model	Male C57BL/6 mice (n = 20, 6-8-week-old, b.w. 18-23 g) were purchased from SJA Laboratory Animal Co Ltd., Changsha, Hunan, China. Mice were given 600 mg/kg D-GalN (Sigma-Aldrich) and 30 ug/kg LPS (Sigma-Aldrich) by intraperitoneal injection. Mice in Sham group were received saline injection. For Fer-1 treatment, mice were received 10 mg/kg Fer-1 at 1 h prior to D-GalN and LPS injection. The wild-type (WT) or HBx-Tg mice were then subjected to D-GalN and LPS administration. For GSK126 treatment, wild-type (WT) or HBx-Tg mice were received GSK126 (150 mg/kg) prior to D-GalN and LPS administration. Click to Show/Hide
Response Description	HBx facilitates ferroptosis in acute liver failure (ALF) via EZH2/H3K27me3-mediated SLC7A11 suppression.

HEPFAL (IncRNA)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[95]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vitro Model	PLC/PRF/5 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0485
Response Description	LncRNA HEPFAL promotes the ubiquitination of SLC7A11, resulting in a decrease in GSH production, which in turn affects the activity of GPX4 and ultimately leads to the occurrence of ferroptosis. And LncRNA HEPFAL has the potential as a target for the diagnosis and treatment of hepatocellular carcinoma.

Heat shock protein 105 kDa (HSPH1)

Regulator Info

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[96]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	GES-1 cells	Normal	Homo sapiens	CVCL_EQ22
	SGC-7901 cells	Gastric carcinoma	Homo sapiens	CVCL_0520
	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
	AGS cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MGC-803 cells	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
In Vivo Model	Four-week-old female BALB/c nude mice were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). For subsequent studies, the nude mice were randomly divided into four groups as follows: sh-Ctrl, sh-ATF2, sh-Ctrl + sorafenib and sh-ATF2 + sorafenib. Approximately 5 x 10⁶ ATF2 knockdown or control MGC803 cells were subcutaneously injected into the axilla of nude mice. Beginning on Day 8, mice in the sorafenib treatment group received 10 mg/kg sorafenib by intraperitoneal injection every 2 days for 3 weeks. Click to Show/Hide
Response Description	Using ChIP-Seq and RNA-Seq, HSPH1 as a target of ATF2 and further validated it by ChIPqPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in gastric cancer cells.

Growth/differentiation factor 15 (GDF15)

Regulator Info

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[97]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MGC-803 cells	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
Response Description	GDF15 knockdown promotes erastin-induced ferroptosis in gastric cancer cell MGC803 by attenuating the expression of SLC7A11 and the function of system Xc-.

gga-miR-129-3p (miRNA)

Regulator Info

Injury of intra-abdominal organs [ICD-11: NB91]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[98]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	LMH cells	Hepatoma	Gallus gallus	CVCL_2580
In Vitro Model	LMH cells	Hepatoma	Gallus gallus	CVCL_2580
Response Description	miR-129-3p affected ferroptosis under Se deficiency conditions through the SLC7A11 pathway. Our research provides a new perspective for the mechanism of Se deficiency on the liver damage.

Frizzled-3 (FZD3)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[86]
Regulator for Ferroptosis	Suppressor
Pathway Response	Wnt signaling pathway			hsa04310
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell invasion
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	KYSE-70 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1356
	hEECs (Human esophageal epithelial cells)
In Vivo Model	BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 10⁶) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. Click to Show/Hide
Response Description	CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathwaysviamiR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11.

ETS translocation variant 4 (ETV4)

Regulator Info

Thyroid cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[99]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell cycle
In Vitro Model	TPC-1 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
	IHH-4 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2960
	Nthy-ori3-1 cells	Normal	Homo sapiens	CVCL_2659
In Vivo Model	Six-week-old BALB/c female nude mice (HFK Bioscience, Beijing, China) were used to perform experimentsin vivo. One hundred forty-four mice were randomly divided into four groups (36 mice in each group). TPC-1 cells were stably transfected with NC shRNA or ETV4-shRNA, and GLAG-66 cells were stably transfected with ETV4-OE or Vector. 5 x 10⁶ cells were injected subcutaneously into the right armpit in mice. After 7 days, the diameter of tumors was measured every 3 days to calculate the tumor volume. Click to Show/Hide
Response Description	The downregulation of ETV4 repressed the tumor development through the low expression of SLC7A11, and the ETV4 overexpression obtained the contrary effects. Overall, knockdown of ETV4 suppressed the papillary thyroid cancer progression by promoting ferroptosis upon SLC7A11 downregulation.

Estrogen receptor (ESR1)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[100]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	ZR-75-1 cells	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
Response Description	SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, the study elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer.

ELAV-like protein 1 (ELAVL1)

Regulator Info

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[55]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	AGS cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MGC-803 cells	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
In Vivo Model	For animal models of gastric subserosal injection, we collected MGC-803 cell lines (5 x 10 cells) that were infected by lentivirus with or without PMAN-OE, and suspended in 40 ul serum-free medium (50% Matrigel). After that, nude mice (six mice per group) were anesthetized by intraperitoneal injection of 100 ul of pentobarbital (1%). After disinfection, the abdominal cavity was opened to expose the greater curvature of the stomach. The tumor suspension (40 ul) was implanted under the serosa of the greater curvature of the stomach of the nude mice through an insulin needle. Click to Show/Hide
Response Description	HIF-1 could act as a protective factor against ferroptosis in gastric cancer (GC) cells. HIF-1 activates PMAN at the transcriptional level, which greatly improves the output of ELAVL1 in the cytoplasm. ELAVL1 directly combines with the AREs of SLC7A11 mRNA 3-UTR and improves the stability of SLC7A11mRNA, thereby increasing the expression of SLC7A11 and reducing the accumulation of ROS and iron in ferroptosis, ultimately promoting the proliferation and development of tumor cells.

E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[100]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	ZR-75-1 cells	Invasive breast carcinoma	Homo sapiens	CVCL_0588
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
Response Description	SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, the study elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer.

Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[82]
Regulator for Ferroptosis	Driver
Pathway Response	Glutathione metabolism			hsa00480
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	TE-1 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	Eca-109 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	HET-1A cells	Normal	Homo sapiens	CVCL_3702
Response Description	ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, 3SLC3A2, and SLC7A11.

DAZ-associated protein 1 (DAZAP1)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[101]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	SMMC-7721 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
	BEL-7402 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In Vivo Model	Male BALB/c nude mice (4-5 weeks, 14-18 g) were purchased from Vital River Laboratories (Beijing, China). We randomly (random number grouping method) divided the mice into five groups: the blank group, the DMSO group, the SF group, the SF + sh-NC group and the SF + sh-DAZAP1 group. For SF-intervention mice, we dissolved 10 mg/kg of SF into 0.2 ml DMSO and injected the mixture intraperitoneally every other day for two weeks. 1 x 10⁷ cells (with or without lentivirus) suspended in 500 ul of ice-cold PBS were subcutaneously injected into the left flank of mice. Click to Show/Hide
Response Description	DAZAP1 knockdown by small interfering RNA markedly inhibited hepatocellular carcinoma (HCC) cell proliferation, migration and invasion. At the mechanistic level, DAZAP1 was identified as a potent inhibitor of ferroptosis and an efficient binding partner of SLC7A11 mRNA.

Cyclic AMP-dependent transcription factor ATF-4 (ATF4)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[40]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Hippo signaling pathway			hsa04390
Cell Process	Cell ferroptosis
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	SNU-398 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0077
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	HLE cells	Hepatocellular carcinoma	Homo sapiens	CVCL_1281
	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
In Vivo Model	SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (10⁶ in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks. Click to Show/Hide
Response Description	In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression.

Cyclic AMP-dependent transcription factor ATF-2 (ATF2)

Regulator Info

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[96]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	GES-1 cells	Normal	Homo sapiens	CVCL_EQ22
	SGC-7901 cells	Gastric carcinoma	Homo sapiens	CVCL_0520
	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
	AGS cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MGC-803 cells	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
	MKN45 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
In Vivo Model	Four-week-old female BALB/c nude mice were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). For subsequent studies, the nude mice were randomly divided into four groups as follows: sh-Ctrl, sh-ATF2, sh-Ctrl + sorafenib and sh-ATF2 + sorafenib. Approximately 5 x 10⁶ ATF2 knockdown or control MGC803 cells were subcutaneously injected into the axilla of nude mice. Beginning on Day 8, mice in the sorafenib treatment group received 10 mg/kg sorafenib by intraperitoneal injection every 2 days for 3 weeks. Click to Show/Hide
Response Description	Using ChIP-Seq and RNA-Seq, HSPH1 as a target of ATF2 and further validated it by ChIPqPCR analysis. HSPH1 can interact with SLC7A11 (cystine/glutamate transporter) and increase its protein stability. Importantly, knockdown of HSPH1 partly reversed the effects caused by ATF2 overexpression on sorafenib-induced ferroptosis in gastric cancer cells.

Coiled-coil domain-containing protein 6 (CCDC6)

Regulator Info

Testicular cancer [ICD-11: 2C80]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[102]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	NTERA-2 cells	Embryonal carcinoma	Homo sapiens	CVCL_0034
	TM4 cells	Normal	Mus musculus	CVCL_4327
	MZ-GC-1 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_4U28
	MZ-GC-2 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_4U29
Response Description	Testicular cancers are among the most common malignancies in young males. The loss of CCDC6 was associated with an enhancement of the xCT/SLC7A11 cystine antiporter expression which, by promoting the accumulation of ROS, interfered with the activation of ferroptosis pathway.

Circ_0067934 (circRNA)

Regulator Info

Thyroid cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[72]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	FTC-133 cells	Thyroid gland follicular carcinoma	Homo sapiens	CVCL_1219
	TPC-1 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
In Vivo Model	BALB/c nude mice (18-20 g, 4-week-old, male) (n = 6) were purchased and applied for the tumor growth analysis of FTC133 cellsin vivo. About 1 x 10⁶ FTC133 cells were transfected with control shRNA or circ_0067934 shRNA and were subcutaneously injected into the left fat pad of mice. After 5 days of injection, we measured tumor growth every 5 days. We sacrificed the mice after 30 days of injection. The tumor volume was calculated by (length x width2)/2. And the tumor weight was calculated at day 30. Click to Show/Hide
Response Description	Circ_0067934 upregulated the expression of the ferroptosis-negative regulator SLC7A11 by sponging and inhibiting miR-545-3p in thyroid cancer cells. The overexpression of SLC7A11 or the inhibitor of miR-545-3p reversed circ_0067934 silencing-regulated thyroid cancer cell proliferation.

CircSnx12 (circRNA)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[90]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In Vitro Model	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
Response Description	circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in ovarian cancer.

CircRPPH1 (circRNA)

Regulator Info

Gastric cancer [ICD-11: 2B72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[81]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MKN45 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
	AGS cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	Hs746T cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0333
	NCI-N87 cells	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
Response Description	circRPPH1 promoted the stemness of gastric cancer cells dependent on the miR-375/SLC7A11. This study provides a potential target for gastric cancer progression based on the circRPPH1/miR-375/SLC7A11 regulatory axis.

CircRHBG (circRNA)

Regulator Info

Ovarian dysfunction [ICD-11: 5A80]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[76]
Regulator for Ferroptosis	Suppressor
Pathway Response	Glutathione metabolism			hsa00480
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	KGN cells	Ovarian granulosa cell tumor	Homo sapiens	CVCL_0375
	SVOG-3e cells	Normal	Homo sapiens	CVCL_IN98
In Vivo Model	We recruited 12 infertility patients (6 PCOS and 6 controls) aged 20 and 38 who underwent in vitro fertilization (IVF) at the Department of Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-Sen University. All patients were treated the antagonist stimulation protocol. Briefly, on cycle day 2, ovarian stimulation was started by daily injection of recombinant FSH (r-FSH) (Gonal-F; Merck Serono). Gonadotropin-releasing hormone (GnRH) antagonist (Cetrotide, 0.25 mg; Merck Serono) injection was started from the day 6 of stimulation. When at least three follicles had reached 17 mm or two follicles had reached 18 mm in diameter, an intramuscular injection of 5,000 IU-10000 IU of human chorionic gonadotropin (hCG) is used for triggering final oocyte maturation. Click to Show/Hide
Response Description	circRHBG inhibits ferroptosis in Polycystic ovary syndrome cells through the circRHBG/miR-515-5p/SLC7A11 axis in PCOS, which may provide new diagnostic molecular markers and therapeutic targets for PCOS.

CircPVT1 (circRNA)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[86]
Regulator for Ferroptosis	Suppressor
Pathway Response	Wnt signaling pathway			hsa04310
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell invasion
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	KYSE-70 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1356
	hEECs (Human esophageal epithelial cells)
In Vivo Model	BALB/c nude male mice of 4 weeks old were purchased from the Model Animal Research Center of Nanjing University (Nanjing, China). After one week of adaptive feeding, EC9706 cells (3 x 10⁶) stably expressing sh-NC and sh-circPVT1, sh-NC + 5-FU and sh-circPVT1 + 5-FU were subcutaneously were injected into the right flank of the nude mice in a serum-free DMEM medium. Click to Show/Hide
Response Description	CircPVT1 regulated the chemosensitivity of esophageal squamous cell carcinoma cells through ROS and Wnt/-catenin pathwaysviamiR-30a-5p/FZD3. Knockdown of circPVT1 promoted chemosensitivity in ESCC by increasing ferroptosis via downregulating GPX4 and SLC7A11.

CircFOXP1 (circRNA)

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[74]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
In Vivo Model	SCID/nude mice (6 weeks old) were ordered from Laboratory Animal Center of Chinese Academy of Sciences (Beijing, China). HT29 cells were co-transfected with sh-circFOXP1 and pCMV-SLC7A11 or empty vector. Cells were digested, 5 x 10⁶ cells were mixed with Matrigel (Corning) and subcutaneously injected into mice. The width and length of tumor were measured at indicated time, and the tumor size was calculated by the formula: 0.5 x length x width2. Mice were then succumbed to death, the tumors were isolated, weighted, and made into paraffin-embedded slices (5-um). The slices were stained with anti-KI67 antibody (Santa Cruz Biotechnology) and subsequent HRP-labeled secondary antibody and captured in a microscope (Leica Microsystems). Click to Show/Hide
Response Description	Mechanically, circFOXP1 increased SLC7A11 expression by directly sponging miR-520a-5p in lung cancer cells. The inhibitor of miR-520a-5p or the overexpression of SLC7A11 reversed circFOXP1 shRNA-induced ferroptosis phenotypes in lung cancer cells.

CircFNDC3B (circRNA)

Regulator Info

Oral squamous cell carcinoma [ICD-11: 2B6E]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[73]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
	SCC-15 cells	Tongue squamous cell carcinoma	Homo sapiens	CVCL_1681
In Vivo Model	The tumorigenicity analysis was conducted in BALB/c nude mice (6-weeks-old, male). The mice were maintained at pathogen-free condition. The 5 x 10⁶ CAL27 cells were treated with control shRNA or circFNDC3B shRNA and subcutaneously injected into the nude mice (N = 5). The mice were sacrificed after 30 days and the tumor volume was calculated using the formula of (length x width2)/2. Click to Show/Hide
Response Description	CircFNDC3B attenuated ferroptosis of Oral squamous cell carcinoma (OSCC) cells and contributed to OSCC progression by regulating the miR-520d-5p/SLC7A11 axis. CircFNDC3B, miR-520d-5p, and SLC7A11 may serve as potential therapeutic targets of OSCC.

CircEPSTI1 (circRNA)

Regulator Info

Cervical cancer [ICD-11: 2C77]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[75]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Ca Ski cells	Cervical squamous cell carcinoma	Homo sapiens	CVCL_1100
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	hCECs (Human cervical epithelial cells)
In Vivo Model	The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 10⁷ cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured. Click to Show/Hide
Response Description	CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis.

CircCDK14 (circRNA)

Regulator Info

Glioblastoma [ICD-11: 2A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[56]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	HEB (Human glial cells)
	SF126 cells	Glioblastoma	Homo sapiens	CVCL_1688
	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
In Vivo Model	4-week-old female BALB/c nude mice were acquired from the National Laboratory Animal Center (Shanghai, China). Overall, 10 mice (n = 5 each group) were implanted with U251 cells stably knockdown circCDK14 by lentiviruses carrying sh-circCDK14 (Wanleibio, China), or control U251 cells with lentiviruses carrying sh-NC (Wanleibio, China). 5 x 10⁶ cells were resuspended in phosphatebuffered saline (100 ul) and Matrigel substrate (100 ul) and injected into the right flank of nude mice. Tumor volume was documented once 7 days after implantation. Click to Show/Hide
Response Description	CircCDK14 promotes the migration, invasion and proliferation of glioma cells in vitroas well as tumorigenesisin vivo. An evaluation of the underlying mechanism revealed that circCDK14 sponged miR-3938 to upregulate oncogenic gene PDGFRA expression. After knockdown of circCDK14 in glioma cells, protein levels of SLC7A11 and GPX4 decreased significantly and Fp became more sensitivity.

CircASAP2 (circRNA)

Regulator Info

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[44]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mKTs (Mouse knee tissues)
	HK-2 (Human renal glomerular endothelial cells)
In Vivo Model	All C57BL/6 mice (5-6 weeks, 18-20 g) were obtained from Animal Testing Center of Qinglongshan (Nanjing, Suzhou, China). DN mice were fed with a high-fat diet (HFD) for 12 weeks and then injected with STZ (30 mg/kg of streptozotocin; Sigma-Aldrich, St Louis, MO, USA) i.p. for 7 consecutive days. Blood glucose levels of mice were measured using 16.7 mmol/l after one week of the final injection. Then, mice were killed under anesthesia and their kidneys taken for analysis after induction of STZ at 4 months. Click to Show/Hide
Response Description	Circular RNA circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/ SLC7A11 by miR-770-5p. Importantly, this research indicated that circ ASAP2 might act as a target for improving the role of ferroptosis in diabetes nephropathy.

Circ0097009 (circRNA)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[92]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell invasion
	Cell metastasis
In Vitro Model	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	BEL-7402 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
	MHCC97-H cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
In Vivo Model	Four-week-old female BALB/c nude mice were subcutaneously inoculated with 2 x 10⁶ cells (5 mice per group). Intratumoral injection (40 uL of si-circ0097009 or negative control siRNA) was administered every 4 days. Mice were sacrificed, and tumor weights were measured after 4 weeks. To establish lung metastases, HepG2 cells were treated with 20 umol/L si-circ0097009. After 48 hours, cells (1 x 10⁵) were intravenously injected into the tail veins of mice (6 mice per group). Click to Show/Hide
Response Description	Circ0097009 acts as a competing endogenous RNA to regulate the expression of SLC7A11, a key regulator of cancer cell ferroptosis, by sponging miR-1261 in hepatocellular cancer. Circ0097009 may be used as a diagnostic biomarker for Hepatocellular carcinoma and as a potential target for HCC therapy.

Circ-BGN (circRNA)

Regulator Info

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[36]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	BT-474 cells	Invasive breast carcinoma	Homo sapiens	CVCL_0179
	SK-BR-3 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0033
In Vivo Model	A total of 24 NOD/SCID mice were purchased from Model Animal Research Center and grown under specific-pathogen-free condition. Mice were randomly divided into three groups (n = 8 per group), BT474-Tr cells were inoculated orthotopically onto the abdominal mammary fat pad. After 1 week, mice were treated with erastin (15 mg/kg intraperitoneal, twice every other day). Erastin was dissolved in 5% DMSO + corn oil (C8267, Sigma). To better dissolve erastin, we warmed the tube at 37 water bath and shook it gently. At the end of the sixth week, all mice were sacrificed, tumor tissues were collected and weighed. Click to Show/Hide
Response Description	Knockdown of circ-BGN inhibited breast cancer cell viability and notably restored its sensitivity to trastuzumab. Further, we found that circ-BGN could directly bind to OTUB1 and SLC7A11, enhancing OTUB1-mediated SLC7A11 deubiquitination and thereby inhibiting ferroptosis.

CERS6-AS1 (IncRNA)

Regulator Info

Thyroid cancer [ICD-11: 2D10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[68]
Regulator for Ferroptosis	Suppressor
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	Nthy-ori3-1 cells	Normal	Homo sapiens	CVCL_2659
	IHH-4 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_2960
	BCPAP cells	Thyroid carcinoma	Homo sapiens	CVCL_0153
	KTC-1 cells	Thyroid carcinoma	Homo sapiens	CVCL_6300
	TPC-1 cells	Thyroid gland papillary carcinoma	Homo sapiens	CVCL_6298
In Vivo Model	Animal experiments were approved by ethics committee of Wuzhou Red Cross Hospital. The TPC-1 cells transfected with sh-CERS6-AS1 or sh-NC were made into cell suspension (2 x 10⁶/ml) with PBS. Then nude mice were randomly divided into sh-CERS6-AS1 group (n = 6) and sh-NC group (n = 6). The mice were subcutaneously inoculated with 200 ul corresponding cell suspension respectively, and then the weight and tumor volume of mice were recorded every other week. After 5 weeks, pentobarbital sodium (120 mg/kg) were intraperitoneally injected to make nude mice euthanasia, and then the tumors were stripped and weighed. Subsequently, immunohistochemistry and RT-PCR were performed. Click to Show/Hide
Response Description	Silencing CERS6-AS1 suppressed cell viability and increased ferroptosis in papillary thyroid cancer. LASP1 was modulated by CERS6-AS1 through sponging miR-497-5p. The expression of Ki67, PCNA, GPX4, and SLC7A11 was inhibited by si- CERS6-AS1 transfection.

BBOX1-AS1 (IncRNA)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease		Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator		[77]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	hESCCs (Esophageal squamous cancer cells)
Response Description	Downregulation of BBOX1-AS1 inhibits cell proliferation, and metastasis accelerates cell apoptosis and ferroptosis in esophageal squamous cell cancer by upregulating miR-513a-3p to reduce SLC7A11 expression. These findings may provide novel insights into the diagnosis and treatment of ESCC.

ATP-binding cassette sub-family C member 5 (ABCC5)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[103]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	SK-HEP-1 cells	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
In Vivo Model	All animal experiments were carried out with the approval of the Southern Medical University Animal Care and Use Committee in accordance with the guidelines for the ethical treatment of animals. Nude nu/nu mice were maintained in a barrier facility in racks filtered with a high-efficiency particulate air filter. The animals were fed an autoclaved laboratory rodent diet. The mice in this study were purchased from the Experimental Animal Centre of Southern Medical University, which is certified by the Guangdong Provincial Bureau of Science. Click to Show/Hide
Response Description	ABCC5 increased intracellular glutathione (GSH) and attenuated lipid peroxidation accumulation by stabilizing SLC7A11 protein, which inhibited ferroptosis. Additionally, the inhibition of ABCC5 enhanced the anti-cancer activity of sorafenib in hepatocellular carcinoma.

ARHGEF26-AS1 (IncRNA)

Regulator Info

Oesophageal cancer [ICD-11: 2B70]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[82]
Regulator for Ferroptosis	Driver
Pathway Response	Glutathione metabolism			hsa00480
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	EC9706 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_E307
	TE-1 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1759
	Eca-109 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_6898
	HET-1A cells	Normal	Homo sapiens	CVCL_3702
Response Description	ARHGEF26-AS1 facilitated ferroptosis but restrained cell growth and positively regulated ADAM23 by sponging miR-372-3p in esophageal squamous cell carcinoma (ESCC). Overexpression of ARHGEF26-AS1 upregulated the protein levels of ADAM23 but depleted the protein levels of GPX4, SLC3A2, and SLC7A11.

Aldo-keto reductase family 1 member C3 (AKR1C3)

Regulator Info

Hepatocellular carcinoma [ICD-11: 2C12]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[41]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Hippo signaling pathway			hsa04390
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell metastasis
In Vitro Model	Hep 3B2.1-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0326
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	MHCC97-H cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_4972
	HCC-LY10 (Human hepatoma cells)
In Vivo Model	To generate murine subcutaneous tumors, 2 x 10⁶ HCC cells were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached approximately 100 mm³ at day 15, mice were randomly allocated into groups and treated with erastin or sorafenib for 2 weeks. Click to Show/Hide
Response Description	Overexpression of AKR1C3 protected against ferroptosis in hepatocellular carcinoma (HCC) cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC.

ADAMTS9-AS1 (IncRNA)

Regulator Info

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[71]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	ES-2 cells	Ovarian clear cell adenocarcinoma	Homo sapiens	CVCL_3509
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
	Caov-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0201
Response Description	ADAMTS9-AS1 regulated SLC7A11 expression through miR-587, thereby affecting ferroptosis, proliferation and migration of Epithelial ovarian cancer cells.

3'-5' RNA helicase YTHDC2

Regulator Info

Lung cancer [ICD-11: 2C25]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[104]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	NCI-H1975 cells	Lung adenocarcinoma	Homo sapiens	CVCL_1511
	NCI-H441 cells	Lung papillary adenocarcinoma	Homo sapiens	CVCL_1561
	NCI-H1650 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1483
	HCC827 cells	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	NCI-H292 cells	Lung mucoepidermoid carcinoma	Homo sapiens	CVCL_0455
	Calu-1 cells	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
In Vivo Model	For xenograft experiments, 1.5 x 10⁷ Doxocycline (Dox)-inducible YTHDC2-expressing H1299 cells were subcutaneously injected into 4-6-week-oldathymic nude mice. At day 14 post inoculation, mice were randomly divided into 2 groups for further administrating with or without Dox (30 mg/kg) every other day. Tumors were assessed after sacrificing the mice at day 28 after implantation. Click to Show/Hide
Response Description	The m6A reader YT521-B homology containing 2 (YTHDC2) has been identified to inhibit lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. YTHDC2 also suppresses SLC3A2 subunit via inhibiting HOXA13-mediated SLC3A2 transcription.

Unspecific Regulator

Acute myeloid leukaemia [ICD-11: 2A60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[105]
Responsed Drug	Indole-3-pyruvic acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	MLL/AF4+ RS4 cells	Adult B acute lymphoblastic leukemia	Homo sapiens	CVCL_0093
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	NIH3T3 cells	Normal	Mus musculus	CVCL_0594
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response Description	Indole-3-pyruvate (I3P) suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program in Childhood acute monocytic leukemia. And I3P elevated the activation of compensatory gene expression as indicated by increased protein amounts of SLC7A11 and HO-1, two important target genes of anti-oxidative stress pathways.

Diffuse large B-cell lymphoma [ICD-11: 2A81]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[106]
Responsed Drug	Imidazole ketone erastin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	SU-DHL-1 cells	Anaplastic large cell lymphoma	Homo sapiens	CVCL_0538
	SU-DHL-2 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_9550
	SU-DHL-6 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_2206
	SU-DHL-8 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_2207
	SU-DHL-10 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1889
	SU-DHL-16 cells	B-cell non-Hodgkin lymphoma	Homo sapiens	CVCL_1890
	A3/Kawakami cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1062
	OCI-LY8 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_8803
	U-937 cells	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
	DoHH2 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1179
	HBL-1 cells	Non-Hodgkin lymphoma	Homo sapiens	CVCL_M572
	U-2932 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1896
	SU-DHL-7 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_4380
	SU-DHL-9 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_4379
	A4/Fukuda cells	B acute lymphoblastic leukemia	Homo sapiens	CVCL_1064
	WSU-NHL cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1793
	SU-DHL-5 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1735
	Karpas-422 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1325
In Vivo Model	NOD/SCID mice (12-weeks of age and ~28 g weight) were weighed before injection and divided into groups of 3 mice per cage. Mice were dosed using three different routes, IP and PO with 50 mg/kg IKE, and IV with 17 mg/kg IKE. Samples were collected at 0, 1, 3, 4, and 8 h from three mice per time point. Additionally, three mice per group were used as controls by administration with equivalent amount of vehicle 1 by IP, PO, and IV, and samples were collected at 8 h. At the appropriate time, mice were sacrificed by CO2 asphyxiation for 3 min and ~0.5 mL of blood was collected via cardiac puncture. Click to Show/Hide
Response Description	Imidazole ketone erastin (IKE) is a potent, selective, and metabolically stable system xc- (SLC7A11)inhibitor. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model.

Osteosarcoma [ICD-11: 2B51]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[107]
Responsed Drug	Tirapazamine		Phase 3	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	143B cells	Osteosarcoma	Homo sapiens	CVCL_2270
	MNNG/HOS Cl #5 cells	Osteosarcoma	Homo sapiens	CVCL_0439
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
Response Description	SLC7A11 overexpression could restored the proliferation and migration abilities inhibited by Tirazamine. Thus, TPZ could inhibit the proliferation and migration of osteosarcoma cells, and induce ferroptosis in part through inhibiting SLC7A11.

Gastrointestinal cancer [ICD-11: 2B5B]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[108]
Responsed Drug	Berberine		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell autophagy
	Cell proliferation
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	TMK-1 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_4384
	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
In Vivo Model	Five-week-old male BALB/c mice were purchased from SLC Japan (Shizuoka, Japan). The animals were maintained in a pathogen-free animal facility under a 12 h light/dark cycle in a temperature (22 )- and humidity-controlled environment, in accordance with the institutional guidelines approved by the Committee for Animal Experimentation of Nara Medical University, Kashihara, Japan, following the current regulations and standards of the Japanese Ministry of Health, Labor and Welfare (approval no. 12924, 5 November 2020). Animals were acclimated to their housing for seven days before the start of the experiment. For the peritoneal dissemination tumor model, CT26 cancer cells (1 x 10⁷ in 0.2 mL per mouse) were injected into the mouse peritoneal cavity. To measure tumor weight, mice were euthanized on Day 12 and the tumors were excised, while the peritoneal tumors were dissected from the intestine, mesenterium, diaphragm, and abdominal wall, with gross removal of non-tumor tissues. The largest tumor was formed on the diaphragm, and paraffin-embedded sections of the excised diaphragmatic tumor were prepared and stained with hematoxylin-eosin. BBR was diluted with distilled water to produce a final concentration of 48 mg/mL. The solutions were ultrasonically treated for 1 h, and fully vortexed for 30 min. BBR solution was administered by free drinking. The intake calculated from the amount of water consumed was 15.2 mg/kg body weight/day. Click to Show/Hide
Response Description	Berberine induces apoptosis and ferroptosis by inhibiting mitochondrial complex I and promoting autophagy, leading to combined cell death in the gastrointestinal cancer and suppressing stemness. BBR induces cell death in GIC cells accompanied by increased mitochondrial superoxide and ACSL4 levels, decreased SLC7A11, and impaired antioxidant mechanisms, indicated by decreased GPX4 expression and decreased GSH.

Gastric cancer [ICD-11: 2B72]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[109]
Responsed Drug	Atranorin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hGCCs (Gastric cancer cells)
In Vivo Model	NOD-scid mice (NOD.CB17-Prkdcscid/NcrCrl) aged 6-7 weeks and weighing 20-22 g were used in the experiment. The animal study was performed at the Shanghai University of Traditional Chinese Medicine with approval from the Institutional Animal Care and Use Committee in accordance with the institutional guidelines. All mice were randomly divided into two groups, and each group consisted of four mice. In experimental group, approximately 1 x 10⁵ GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul Atranorin@SPION (10 mg/kg) every 2 days. In control group, approximately 1 x 10⁵ GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul SPION (10 mg/kg) alone every 2 days. After 2 months, the mice were sacrificed, and their tumors were excised. Click to Show/Hide
Response Description	Atranorin@SPIONs significantly reduced the 5-hydroxymethylcytidine modification level of GPX4 and SLC7A11 mRNA 3' untranslated region in gastric cancer cells. This study revealed the molecular biological mechanism by which Atranorin@SPION inhibit the in vitro and in vivo activity of GCSCs, that is, Atranorin@SPION reduced the expression of members of the Xc-/GPX4 axis and reduced their mRNA 5-hydroxymethylcytidine modification, finally induced ferroptosis of GCSCs.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[110]
Responsed Drug	Actinidia chinensis Planch		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
In Vitro Model	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
In Vivo Model	Wild type AB strain of zebrafish (Danio rerio) was obtained from Southern Medical University. The HGC-27 cells labeled with EGFP were resuspended in PBS in the concentration of 5*10⁷/ml. 10 nl cell suspension containing approximately 300 cells were loaded into capillary needles and injected into the abdominal perivitelline space of zebrafish embryos by a nanoliter injector (Narishige, Tokyo, Japan). After injection, the tumor-bearing embryos were transferred into a 24-well plate and acclimated in embryo water at 35 for 24 h and then incubated at 0, 90, 180 mg/ml ACP decoction for 48 h. Click to Show/Hide
Response Description	Actinidia chinensis Planch (ACP) increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype.

Colon cancer [ICD-11: 2B90]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[111]
Responsed Drug	Pt3R5G		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	RKO cells	Colon carcinoma	Homo sapiens	CVCL_0504
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	NCM460 cells	Normal	Homo sapiens	CVCL_0460
In Vivo Model	Five-week-old male BALB/c-nude mice from Central Laboratory of Animal, Xi'an Jiaotong University Health Science Center were housed 4 per cage under controlled temperature (23 ± 2 ), a 12 h/12 h light/dark cycle with ad libitum access to food and water and specific pathogen-free conditions. Twelve BALB/c-nude mice were randomly divided into three groups (control, 25 mg/kg, 50 mg/kg). 1 x 10⁶ RKO cells were subcutaneously injected into either side of the same mice dorsal flanks. After 14 days, animals then received Pt3R5G (25 mg/kg, 50 mg/kg) byintraperitoneal injectionfor 15 days. The weight of mouse and tumor nodules sizer were measured every 3 days for 29 days. Click to Show/Hide
Response Description	Pt3R5G significantly down-regulated SLC7A11 expression and up-regulated TFR1 in RKO cells. Pt3R5G inhibits cell proliferation through inducing ferroptosis by down-regulating SLC7A11 in colon cancer.

Colorectal cancer [ICD-11: 2B91]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[112]
Responsed Drug	Propofol		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
In Vivo Model	CT26 (1 x 10⁵ cells/100 uL) were injected into thetail veinof male BALB/c mice. Then the mice were randomly divided into saline, vehicle, propofol, and sevoflurane groups (n = 5 per group). Saline, fat emulsion (as vehicle control of propofol), and propofol (200 mg/kg) were intraperitoneally injected, while sevoflurane (1.8-2.0%) was administered by inhalation for 2 h. In another set of experiments, coloncancer cells (CT26 and HT29) were pretreated with two doses of propofol (5 ug/mL, 10 ug/mL) or fat emulsion (as vehicle control of propofol) in a cell culture medium for 2 h. After washing with phosphate-buffered saline (PBS), the cells were harvested,counted on a hemacytometer and prepared. Cells (CT26: 1 x 10⁵ cells/100 uL, HT29: 1 x 10⁶ cells/100 uL) were finnally injected into mice through the tail vein.Lung metastasiswas detected via hematoxylin and eosin staining (HE) or ex vivo bioluminescence imaging. Click to Show/Hide
Response Description	Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting colorectal cancer cell metastasis through Nrf2-mediated ferroptosis inhibition.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[113]
Responsed Drug	2-Imino-6-methoxy-2H-chromene-3-carbothioamide		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	mTOR signaling pathway			hsa04150
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	DLD-1 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
In Vivo Model	Five-week-old female BALB/c nude mice were purchased from Beijing Weitong Lihua Experimental Animal Technical Co., Ltd. (Beijing, China). The mice were randomly assigned to the treatment and control groups until the tumor size reached approximately 100 mm³. The mice in the treatment group were injected with 0.174 mg/mL IMCA (100 uL), and those in the control group were injected with an equal volume of normal saline. The nude mice were euthanized, and samples were obtained from their tumor, heart, hepar, kidney, and blood after 33 days of IMCA treatment. Click to Show/Hide
Response Description	2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) significantly induced the ferroptosis of colorectal cancer cells. Mechanistically, IMCA downregulated the expression of SLC7A11 and decreased the contents of cysteine and glutathione, which resulted in reactive oxygen species accumulation and ferroptosis.
Experiment 3 Reporting the Ferroptosis-centered Disease Response of This Regulator				[114]
Responsed Drug	Talaroconvolutin A		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	5 x 10⁶ HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm³, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days. Click to Show/Hide
Response Description	Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy.

Hepatocellular carcinoma [ICD-11: 2C12]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[115]
Responsed Drug	Sorafenib		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	SNU-182 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0090
	SNU-449 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
In Vivo Model	A total of 20 male Balb/c nude mice aged 6-8 weeks were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). Five million Huh7 cells were inoculated into the right flanks of the mice. When the tumor size reached 80-100 mm³, the mice were randomly divided into four groups and administered artesunate (30 mg/kg mouse weight) alone, sorafenib (20 mg/kg mouse weight) alone, a combination of artesunate and sorafenib, or the same volume of PBS by gavage every other day. Click to Show/Hide
Response Description	Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in hepatocellular carcinoma treatment.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[116]
Responsed Drug	Necrostatin-1		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1 cells	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
Response Description	Necrostatin-1 potentiated sulfasalazine-induced expression of SLC7A11, a catalytic subunit of system xc- in these cells. And necrostatin-1 Prevents Ferroptosis in a RIPK1- and IDO-Independent Manner in Hepatocellular Carcinoma.

Lung cancer [ICD-11: 2C25]

In total 5 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[117]
Responsed Drug	Ginkgetin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	SPC-A1 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In Vivo Model	Briefly, when tumours on transplanted nude mice reached around 100 mm³, the mice were randomized divided into eight groups: control, ginkgetin, DDP, ginkgetin + DDP, UAMC 3203, ginkgetin + UAMC 3203, DDP + UAMC 3203, ginkgetin + DDP + UAMC 3203. Both DDP (3 mg/kg) and ginkgetin (30 mg/kg) were administered by intraperitoneal injection, with 2 - 3 times per week and once per day, respectively. UAMC 3203 (10 mg/kg) was administered 5 days/week by intraperitoneally injection. Tumour size and body weight were measured 3 times per week. After dosing 31 days, the nude mice were sacrificed, and tumours were removed and weighed. Click to Show/Hide
Response Description	The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured non-small cell lung cancer (NSCLC) cells.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[118]
Responsed Drug	Sulforaphane		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Glutathione metabolism			hsa00480
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	H69 cells	Normal	Homo sapiens	CVCL_8121
	NCI-H82 cells	Lung small cell carcinoma	Homo sapiens	CVCL_1591
	H69AR cells	Lung small cell carcinoma	Homo sapiens	CVCL_3513
Response Description	Sulforaphane (SFN)-induced cell death was mediated via ferroptosis and inhibition of the mRNA and protein expression levels of SLC7A11 in small-cell lung cancer (SCLC) cells. The anticancer effects of SFN may provide novel options for SCLC treatment.
Experiment 3 Reporting the Ferroptosis-centered Disease Response of This Regulator				[119]
Responsed Drug	Capsaicin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H23 cells	Lung adenocarcinoma	Homo sapiens	CVCL_1547
Response Description	Capsaicin inhibited the proliferation of A549 and NCI-H23 cells and induced ferroptosis by inactivating SLC7A11/GPX4 signaling. Capsaicin could be used as a potential anticancer agent in the treatment of non-small cell lung cancer.
Experiment 4 Reporting the Ferroptosis-centered Disease Response of This Regulator				[120]
Responsed Drug	Manoalide		Phase 2	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	H157 cells	Oral cavity Squamous cell carcinoma	Homo sapiens	CVCL_2458
	HCC827 cells	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In Vivo Model	The LSL-KrasG12D mouse model was obtained from the Jackson Laboratory (Sacramento, CA). Adeno-Cre (Genechem, Shanghai, China) was introduced into the trachea of mice at a dose of 1.25 x 10₁₁ PFU in a total volume of 50 uL. Tumor tissues from 12-week post-infection mice were washed with cold PBS, cut into small pieces, and washed with DMEM/F12 (containing 1 x Glutamine, 10 mM HEPES, and antibiotics), digested with collagenase I and IV for 0.5-1 h at 37. After washing twice with DMEM/F12 and centrifugation (500 g, 5 min), the dissociated cells were seeded into growth factor-reduced matrigel (Corning, #356237) at 37 for 30 min. Click to Show/Hide
Response Description	Manoalide (MA) induces ferroptosis by suppressing the NRF2-SLC7A11 axis and mitochondrial Ca2+overload induced-FTH1 pathways to promote the sensitivity of osimertinib-resistant lung cancer cells to osimertinib.
Experiment 5 Reporting the Ferroptosis-centered Disease Response of This Regulator				[121]
Responsed Drug	XAV939		Preclinical	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
In Vitro Model	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
Response Description	The downregulation of the lncRNA MIR503HG induced by XAV939 may serve an important role in suppressing the progression of non-small cell lung cancer via sponging miR1273c, to downregulate its target SOX4. Furthermore, the downregulation of SLC7A11 induced by XAV939 may inhibit NSCLC development via participation in the ferroptosis pathway.

Breast cancer [ICD-11: 2C60]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[122]
Responsed Drug	Sulfasalazine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
Response Description	The combined effects of vorinostat with salazosulfapyridine (SASP) depend on the accumulation of ROS caused by a decrease in intracellular GSH levels, possibly due to SASP-mediated inhibition of xCT. xCT (coded by the SLC7A11 gene), a light chain subunit of the glutamate-cystine antiporter system Xc(-) in Breast adenocarcinoma.

Uterine serous carcinoma [ICD-11: 2C72]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[123]
Responsed Drug	Sulfasalazine		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	hUPSCs (Human uterine serous papillary carcinoma-1 cells)
	Abcam HeLa ERGIC2 KO cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_B1RG
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In Vivo Model	The mean weight of the mice at the start was 19.4 ± 0.87 g. To generate the subcutaneous xenograft model, USPC1 (5 x 10⁶ cells) or PTX1 (5 x 10⁶ cells) were suspended in 200 ul of PBS following determination of cellular viability and injected into the subcutaneous tissue of 6-week-old female Crj:SHO-PrkdcscidHrhr hairless SCID mice (n = 2) (Charles River Laboratories Inc.). Tumor formation was visually confirmed in mice inoculated with USPC1 cells, but not in those inoculated with PTX1 cells, thus the animal study was performed using USPC1 cells. The recipient mice were monitored for general health status and presence of subcutaneous tumors once a week. Click to Show/Hide
Response Description	The effect of the xCT (SLC7A11) inhibitor, sulfasalazine on cytotoxicity was stronger in paclitaxel-resistant uterine serous carcinoma (USC) cells compared with that in paclitaxel-sensitive USC cells. Furthermore, the synthetic lethal interaction between the accumulation of ROS and the activation of the Ras effector, JNK, induced cell-proliferation inhibition and ferroptotic cell death in paclitaxel-resistant USC cells.

Ovarian cancer [ICD-11: 2C73]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[124]
Responsed Drug	Norcantharidin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In Vitro Model	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
In Vivo Model	Athymic nu/nu female mice aged 6-8 weeks (n = 9; mean weight, 20.21 ± 1.54 g) were purchased from the specific pathogen SPF (Beijing) Lab Animals Technology Co. Ltd. Mice were housed in a temperature- and humidity-controlled environment (20-24 , 45-55% humidity), with free access to food and water and in groups of three. All procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC ID: 17-3256) at Nantong University and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. Click to Show/Hide
Response Description	Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following norcantharidin (NCTD) treatment. Collectively, NCTD may represent a potent anticancer agent in ovarian cancer cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/HO-1/GPX4/xCT axis.

Diabetes mellitus [ICD-11: 5A10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[125]
Responsed Drug	Cryptochlorogenic acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	INS-1 cells	Insulinoma	Rattus norvegicus	CVCL_0352
In Vivo Model	Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful. Click to Show/Hide
Response Description	Cryptochlorogenic acid (CCA) functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. System xc- which is composed of SLC7A11 and SLC3A2, served as the provider of GSH synthesis.

Ovarian dysfunction [ICD-11: 5A80]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[126]
Responsed Drug	N-acetylcysteine	Approved	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
	Cell differentiation
In Vitro Model	hPTs (Human placental tissues)
In Vivo Model	Adult Sprague-Dawley rats (70 days old) of both sexes were purchased from the Laboratory Animal Centre of Harbin Medical University, Harbin, China. Before the experiment, female rats were allowed to acclimatize for a minimum of 1 week and then were monitored daily by vaginal lavage to determine the stage of the estrous cycle as previously described (Zhanget al., 2016). Pregnancy was achieved by housing female rats on the night of proestrus with fertile males of the same strain at a 2:1 ratio. Confirmation of mating was performed the morning after by the presence of a vaginal plug, and this was considered as GD 0.5. The rats were sacrificed between 8:00 a.m. and 9:00 a.m. hours on GD 14.5. Click to Show/Hide
Response Description	Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical polycystic ovary syndrome (PCOS)-like rat model. N-acetylcysteine treatment results in increased mRNA expression of Aifm2, a negative regulator of GPX4-independent ferroptosis in the placenta. Moreover, NAC reverses HAIR-induced uterine and placental ferroptosis through activation of the Slc7a11/GSH/GPX4 axis.

Cognitive disorder [ICD-11: 6D71]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[127]
Responsed Drug	Liraglutide	Approved	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mHNs (Mouse hippocampal neurons)
In Vivo Model	Male diabetic db/db mice and nondiabetic littermate db/m mice that were 4 weeks of age were purchased from Changzhou Cavens Experimental Animal Co., Ltd. After 1week of adaptive feeding, 20 db/db mice were randomly divided into two groups: a model group (db/db, n = 10) and a treatment group (LIRA, n = 10). Another 10 db/m mice were used as the control group (db/m, n = 10). After feeding to 10weeks old, the LIRA group was given liraglutide (CSN11311, CSNpharm, China) diluent (200 ug/kg/d) by intraperitoneal injection for 5 weeks, with equivoluminal 0.9% saline intraperitoneally administered to the other two groups. Click to Show/Hide
Response Description	Liraglutide was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetes-induced cognitive dysfunction and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.

Parkinson disease [ICD-11: 8A00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[128]
Responsed Drug	Paraquat		Investigative	Drug Info
Pathway Response	Apoptosis			hsa04210
	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell apoptosis
In Vitro Model	SH-SY5Y cells	Neuroblastoma	Homo sapiens	CVCL_0019
In Vivo Model	Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments. Click to Show/Hide
Response Description	Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence.

Intracerebral hemorrhage [ICD-11: 8B00]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[129]
Responsed Drug	Baicalin		Terminated	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC12 cells	Adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481
In Vivo Model	A total of 60 male C57BL/6 mice (10weeks old, 25-28g) were purchased from Guangzhou University of Chinese Medicine Experimental Animal Center (Guangzhou, China). The mice were maintained with enough food and water at 24, 60% relative humidity and 12/12h light/dark cycle. The mice were randomly divided into three groups: sham operation group (Sham), ICH model group (Mod) and baicalin group (Bai) (n = 20/group). Baicalin was suspended in 0.5% carboxymethylcellulose sodium solution. Given the extremely low solubility of baicalin, the concentration of baicalin solution was 0.5 mg/ml. To achieve 20 mg/kg/day dosage, the baicalin solution was administered to the mice in the Bai group by oral route twice at an interval of 1 h within 2 h after ICH injury onset. The remaining two groups received an equal volumes of saline through oral gavage. Since the second day after ICH, mice in the Bai group received 20 mg/kg of baicalin solution while those in the remaining two groups received equal volumes of saline once a day for three consecutive days. Click to Show/Hide
Response Description	Baicalin significantly increased the mRNA expression of GPX4 and SLC7A11 in the perihematoma brain tissues of intracerebral hemorrhage (ICH) model mice. Baicalin can inhibit the development of ferroptosis in ICH. Baicalin is a potential therapeutic drug for ICH treatment.

Cerebral ischemia [ICD-11: 8B10]

In total 2 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[130]
Responsed Drug	Galangin	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mHNs (Mouse hippocampal neurons)
In Vivo Model	Male gerbils weighing 70-90 g (12 weeks) were selected for this study. Gerbils were anesthetized with 7% chloral hydrate (350 mg/kg) and the bilateral common carotid arteries were occluded using artery clips. After 5 min, the clips were removed to restore cerebral blood flow. After the operation, place the gerbil on an electric blanket to keep the gerbil's body temperature. The sham group underwent the same surgical procedure without ligation of carotid arteries and was given an equal volume of physiological saline as in the treated groups. The model + galangin (Jiangsu Yongjian Pharmaceutical Technology, 548-83-4, Purity: >=98% (HPLC)) groups underwent the same procedure as the model group and then were received galangin at 25, 50, or 100 mg/kg/day for two continuous weeks. Click to Show/Hide
Response Description	Gerbils treated with galangin after ischemia-reperfusion (I/R) injury showed significant improvements in learning and memory. In addition, galangin treatment reduced the levels of lipid peroxide in the brains of gerbils that underwent I/R as well as reduced the amount of cell death and increased the expression of SLC7A11 and glutathione peroxidase 4 (GPX4).
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator			[131]
Responsed Drug	Chrysin	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups (200, 100, and 50 mg/kg), and a positive drug group (Ginaton, 21.6 mg/kg). The CIRI model was induced in rats by transient middle cerebral artery occlusion (tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. Click to Show/Hide
Response Description	The chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by cerebral ischemia-reperfusion injury.

Cerebral ischaemic stroke [ICD-11: 8B11]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[132]
Responsed Drug	Kaempferol	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mPCNs (Mouse primary cortical neurons)
Response Description	Kaempferol provides protection from OGD/R-induced ferroptosis, at least in part, by activating Nrf2/SLC7A11/GPX4 signaling pathway. Therefore, pharmacological inhibition of ferroptosis may be an attractive therapeutic target for the treatment of ischemic stroke.

Cardiomyopathy [ICD-11: BC43]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[133]
Responsed Drug	Canagliflozin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Male C57BL/6J mice aged 6-8 weeks with weights of 18-20 g were obtained from the Slack Laboratory Animal Co., Ltd. (Shanghai, China). Mice were allowed to acclimatize in the laboratory environment for 1 week before the beginning of the experiment. DCM model establishment: The mice were given a single intraperitoneal injection of 150 mg/kg 1% streptozotocin (STZ, V900890, Sigma, USA, dissolved in 0.1 mol/L sodium citrate buffer, pH = 4.4 - 4.6). Mouse blood from the tail vein was collected in each group of the model mice and tested by glucose meter (Accu-Chek Performa test strips, Roche, Accu-Chek Performa Combo, Roche, USA) on day 3, 5 and 7 after injection. Click to Show/Hide
Response Description	Canagliflozin (Cana) promotes upregulation of SLC7A11 and downregulation of TfR1 and FTN-H, which protect the cardiomyocytes from ferroptosis. These finding suggests that Cana inhibit ferroptosis by balancing cardiac iron homeostasis and promoting the system Xc/GSH/GPX4 axis in diabetic cardiomyopathy.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[134]
Responsed Drug	Liquiritin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	The set of animal experiments was designed to evaluate the effectiveness of liquiritin on doxorubicin-induced cardiotoxicity as were as ferroptosis were explored. Mice were randomly divided into 5 groups: (1) the control group; (2) doxorubicin group; (3) the doxorubicin plus liquiritin group (20 mg/kg); (4) the doxorubicin plus liquiritin group (40 mg/kg); (5) the doxorubicin plus liquiritin group (80 mg/kg) (Han et al.2022; Mou et al.2021). The control group and doxorubicin group were given equal volume of 0.5% sodium carboxymethylcellulose; the doxorubicin plus liquiritin groups were given different doses of liquiritin (0.5%) sodium carboxymethylcellulose co-suspension) by intragastric administration 7 days in advance once a daily. On day 8, groups (2), (3), (4), and (5) were given a single intraperitoneal injection of 15 mg/kg of DOX to establish a model of doxorubicin-induced cardiotoxicity; and group (1) was given an equal volume of saline intraperitoneally. Click to Show/Hide
Response Description	Liquiritin can protect the doxorubicin-induce mice's cardiotoxicity, and its beneficial effect is related to the reduction of ferroptosis through a mechanism involving the regulation of the SLC7A11/GPX4 pathway.

Congestive heart failure [ICD-11: BD10]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[135]
Responsed Drug	Atorvastatin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	8-week C57BL/6J male mice purchased from Comparative Medicine Center of Yangzhou University were retained with unrestricted access to sterilized diet and water at standard bio-clean laboratory settings (Experimental Animal Center of College of Veterinary Medicine of Yangzhou University). Animals were randomly divided into four groups(n = 6-8 mice per group): control group or ISO group: injected with saline or ISO (5 mg/kg) subcutaneously for 14 days and, meanwhile, received vehicle saline via gavage for 14 days respectively; ATV (Pfizer,USA) group or ISO + ATV group: injected with saline or 5 mg/kg ISO (Sigma, USA) subcutaneously for 14 days and, meanwhile, received 20 mg/kg ATV via gavage for 14 days respectively. Click to Show/Hide
Response Description	Atorvastatin showed significantly protective effects through suppressing the activation of ferroptosis related signaling, as evidenced by decreasing the mRNA levels of PTGS2 (a marker of ferroptosis), contents of malonaldehyde and protein levels of NOX4 and increasing the contents of glutathione (GSH), the ratio of GSH/GSSG and protein levels of GPX4 and SLC7A11. ATV reduced cardiac hypertrophy and fibrosis and accumulation of iron in heart failure.

Cardiovascular diseases [ICD-11: BE2Z]

In total 2 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[136]
Responsed Drug	Astragaloside IV	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	HUVECs (Human umbilical vein endothelial cells)
Response Description	Astragaloside IV partially upregulated the levels of SLC7A11 and GPX4 expression which were reduced by LPC. The LPC-suppressed proliferation and LPC-induced apoptosis and senescence of endothelial cells were greatly attenuated by AS-IV treatment. In conclusion, AS-IV could serve as a novel drug for treating ferroptosis-related cardiovascular diseases.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator			[137]
Responsed Drug	Sesamin	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	rHTs (Rat hippocampal tissues)
In Vivo Model	Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. Click to Show/Hide
Response Description	Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis.

Liver fibrosis [ICD-11: DB93]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[138]
Responsed Drug	Chrysophanol		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HSC-T6 cells	Normal	Rattus norvegicus	CVCL_0315
Response Description	Chrysophanol significantly induced HBx-transfected HSC-T6 death by inducing ferroptosis, as demonstrated by lipid ROS accumulation and upregulation of expression of ER markers, such as Bip, CHOP, and p-IRE1, and ferroptotic markers, such as GPX4 and SLC7A11. Therefore, chrysophanol may exert ferroptotic effects on activated HSCs to prevent liver fibrosis.

Ischemia/reperfusion injury [ICD-11: DB98]

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[139]
Responsed Drug	Salidroside		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
In Vivo Model	Following endotracheal intubation, mice were ventilated with room air at a rate of 120 cycles/min and atidal volumeof 7 mL/kg (MiniVent, Harvard Apparatus, USA). To induce ischemia, mice underwent left thoracotomy, and the left pulmonary hilum was blocked for 60 min with a microvascular clamp. After ischemia, the coronary artery was reperfused for 120 min by removing the clamp. The mice were euthanized at the end of the experiment through CO2 asphyxiation and cervical dislocation. Next, bronchoalveolar lavage fluid (BALF), blood, and lung samples were collected for testing. Click to Show/Hide
Response Description	Salidroside postconditioning attenuates ferroptosis-mediated lung ischemia-reperfusion injury by activating the Nrf2/SLC7A11 signaling axis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[140]
Responsed Drug	Dimethyl fumarate		Approved	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	AML12 cells	Normal	Mus musculus	CVCL_0140
In Vivo Model	The mice were randomly divided into four groups of six: sham + vehicle, sham + DMF, IR + vehicle, and IR + DMF. The mice were supplemented with DMF at a concentration of 100 mg/kg or DMSO by daily oral gavage for a week before surgery, as previously reported. As stated in a prior study, the partial warm liver IRI model was developed. Briefly, the sham group only had free hepatic portal blood vessels after laparotomy, and the blood flow was not obstructed. As for the hepatic IR group, the blood supply to the left and mid-hepatic lobes was blocked, resulting in 70% mouse liver IRI for 90 min. The mice were put on a heated blanket after surgery in order to maintain body temperature and monitor vital signs. Blood supply was restored for 6 h. Died mice were eliminated for testing prior to sample collection. The mice were euthanized after the sample were obtained. The same experimenter carried out all surgeries. Click to Show/Hide
Response Description	NRF2 knockdown notably decreased the expression of SLC7A11 and HO-1 and blocked the anti-ferroptosis effects of dimethyl fumarate (DMF). DMF inhibits ferroptosis by activating the NRF2/SLC7A11/HO-1 axis and exerts a protective effect against hepatic ischemia-reperfusion injury.

Chronic kidney disease [ICD-11: GB61]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[141]
Responsed Drug	Aspirin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
In Vivo Model	These mice were on eight weeks old male DBA/2J background (n = 36, HFK Bioscience, Beijing, China). They were randomized one of the six groups: control normal mice group (NC); diabetic mice group (DM); diabetic mice group (Fer-1), who intraperitoneal injected Fer-1 (Selleck, Houston, TX, USA); diabetic mice group (vehicle-P), who intraperitoneal injected 1% dimethyl sulfoxide (DMSO); diabetic mice group (As), who intragastric administrated Aspirin (Solarbio, Beijing, China); diabetic mice group (vehicle-G), who intragastric administrated 0.5% sodium carboxymethyl cellulose (Na-CMC; Solarbio, Beijing, China). Diabetes models were induced with 5 consecutive days of a single intraperitoneal injection of streptozotocin 40 mg/kg (dissolved in 0.1 M citrate buffer, pH 4.5; SigmaAldrich, St Louis, MO, USA). Control mice only was injected the same volume of citrate buffer. In the Fer-1 or vehicle-P groups, the diabetic mice were treated respectively with Fer-1 (2.5 umol/kg, dissolved in 1% DMSO) or 1% DMSO during the duration of treatment for 12-week every day. And in the AS and vehicle-G groups, the diabetic mice were treated respectively with aspirin (50 mg/kg, dissolved in 0.5% Na-CMC) or 0.5% Na-CMC for 12-week every day. Click to Show/Hide
Response Description	Aspirin can upregulate SLC7A11 and GPX4 expression by suppressing COX2. Our results demonstrated that ferroptosis in renal tubular cells contributes to Diabetic kidney disease (DKD) development and that diabetes-related ferroptosis was inhibited through the downregulation of COX2 by aspirin, thus retarding the progression of DKD.

Lung injury [ICD-11: NB32]

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[142]
Responsed Drug	Astragaloside IV		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hT2AECs (Type II alveolar epithelial cells)
In Vivo Model	The animals were randomly assigned to six groups (7 mice in each) as follows: (I) Normal saline (NS) group, (II) Ast-IV 100 mg/kg (Ast) group, (III) PM2.5 group, (IV) Ast-IV 50 mg/kg + PM2.5 (Ast-L) group, (V) Ast 100 mg/kg + PM2.5 (Ast-H) group, and (VI) Ast-IV 100 mg/kg + erastin 20 mg/kg + PM2.5 (Era) group. Based on our previous results, this study adopted anintraperitoneal injection(i.p.) of Ast-IV (dissolved in normal saline containing 0.1% DMSO for preventive treatment. After all the mice were adaptively fed for 5 days, in the NS and PM2.5 groups, mice received the normal saline containing 0.1% DMSO viai.p.once a day for the next three consecutive days. Similar to the NS group, in the Ast, Ast-H, and Era groups, mice received Ast-IV (100 mg/kg) viai.p. Ast-L group received Ast-IV (50 mg/kg) viai.p. To evaluate the effect of Ast-IV on ferroptosis in PM2.5-induced lung injury, we used the ferroptosis agonist erastin to activate ferroptosisin vivo. In the Era group, mice received erastin (20 mg/kg, 10% DMSO + 40% PEG300 + 5%Tween80 + 45% normal saline) 30 min before each preventive treatment of Ast-IV. Click to Show/Hide
Response Description	Astragaloside IV (Ast-IV) reduced the lung wet-dry ratio and the levels of interleukin 6 (IL-6), tumor necrosis factor- (TNF-) and interleukin 1 (IL-1) in serum. Ast-IV could also improve the oxidative stress level in BALF, restore the GSH level in the lung tissue, and reduce the iron content in the lung tissue. Western blot outcomes revealed that Ast-IV regulated the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to protect PM2.5-mediated lung injury.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[143]
Responsed Drug	Lipopolysaccharide		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
In Vivo Model	The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. Click to Show/Hide
Response Description	The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues.
Experiment 3 Reporting the Ferroptosis-centered Disease Response of This Regulator				[143]
Responsed Drug	Ferrostatin-1		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
In Vivo Model	The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. Click to Show/Hide
Response Description	The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues.

Injury of intra-abdominal organs [ICD-11: NB91]

In total 1 item(s) under this disease			Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator			[144]
Responsed Drug	Lycopene	Investigative	Drug Info
Pathway Response	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mSCs (Mouse splenocytes)
In Vivo Model	Three-week-old specific pathogen-free ICR (Institute of Cancer Research) male mice (weights of 18-22 g) were provided by Liaoning Changsheng Biotech Co. Ltd. The mice were housed under conditions at 22 ± 2 with 35-65% humidity and a light/dark cycle of 12 h/12 h in the cage. The animals were quarantined for a week before formal experiments, then randomly divided into seven groups: vehicle control group (Vcon), control group (Con), 5 mg/kg BW/d Lyc group (Lyc), 500 and 1000 mg/kg BW/d DEHP group (D5 and D10, respectively), DEHP + Lyc group (DL5 and DL10, respectively) (n = 20). The animals were exposed to DEHP via oral gavage, which lasted for 28 d, and then sacrificed after being anesthetized. Click to Show/Hide
Response Description	DEHP disrupted the GSH metabolism via the xc/ GPX4 antioxidant system and, subsequently, caused the ferroptotic cell death, but Lycopene (Lyc) could effectively mitigate DEHP-induced damage to the antioxidant system. These findings indicated that Lyc may be an effective strategy for the prevention of DEHP-induced splenic toxicity via the regulation of ferroptosis.

Health [ICD-11: N.A.]

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[146]
Responsed Drug	T-2 Toxin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vitro Model	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
Response Description	SLC7A11 overexpression significantly rescued the enhanced ferroptosis caused by T-2 toxin. T-2 toxin induces ferroptosis by downregulating SLC7A11 expression. Ferroptosis mediates T-2 toxin-induced cytotoxicity by increasing ROS and downregulating SLC7A11 expression.

Ubiquitin-fold modifier 1 (UFM1)

Regulator Info

Metformin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[1]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Breast cancer [ICD-11: 2C60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	HCC1937 cells	Breast ductal carcinoma	Homo sapiens	CVCL_0290
	Bcap37 cells	Breast carcinoma	Homo sapiens	CVCL_0164
	HBL-100 cells	Normal	Homo sapiens	CVCL_4362
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	BT-549 cells	Invasive breast carcinoma	Homo sapiens	CVCL_1092
In Vivo Model	T47D xenografts were established in 5-week-old nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 10⁷ cells mixed with Matrigel (BD Biosciences) at 1:1 ratio (volume) into the abdominal mammary fat pad. When the tumor reached 50-100 mm³, the mice were assigned randomly into different treatment groups (DMSO, Metformin, SAS, and Metformin + SAS groups). Metformin (200 mg/kg/day) was provided in drinking water. Sulfasalazine was dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 250 mg/kg once a day. Click to Show/Hide
Response Description	Metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc-inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells.

Ubiquitin thioesterase OTUB1 (OTUB1)

Regulator Info

Solasonine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[2]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	CFPAC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_1119
In Vivo Model	For xenograft assays, we subcutaneously injected 1 x 10⁶ PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment. Click to Show/Hide
Response Description	Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis.

Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)

Regulator Info

Erastin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[3]
Regulator for Ferroptosis	Driver
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 10⁶ cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. Click to Show/Hide
Response Description	SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy.

Cisplatin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[3]
Regulator for Ferroptosis	Driver
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo. There were six mice in each group. A total of 2 x 10⁶ cells were seeded subcutaneously into 6-week-old BALB/ C-Nu Male mice. Tumor width (W) and length (L) at different experimental time points were measured with calipers, and tumor growth was monitored. Click to Show/Hide
Response Description	SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 ( TNFAIP3) SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy.

Transcription factor AP-2-alpha (TFAP2A)

Regulator Info

Solasonine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[2]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	CFPAC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_1119
In Vivo Model	For xenograft assays, we subcutaneously injected 1 x 10⁶ PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment. Click to Show/Hide
Response Description	Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis.

Signal transducer and activator of transcription 3 (STAT3)

Regulator Info

Bavachin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[4]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Osteosarcoma [ICD-11: 2B51]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MG-63 cells	Osteosarcoma	Homo sapiens	CVCL_0426
In Vitro Model	HOS cells	Osteosarcoma	Homo sapiens	CVCL_0312
Response Description	Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression.

rno-miR-23a-3p (miRNA)

Regulator Info

GW4869 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[5]
Regulator for Ferroptosis	Driver
Responsed Disease	Supraventricular tachycardia [ICD-11: BC81]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
	rCFs (Rat cardiac fibroblasts)
In Vivo Model	Eighteen beagles, randomly divided into three groups, both sexes and an average age of 1 year, weighing 7.5 ± 1.5 kg, were used for the study as follows: Sham group (n = 6), Pacing group (n = 6), and GW4869 + Pacing group (n = 6). Each beagle canine was given an intramuscular injection of 25 mg/kg ketamine sulfate before being premedicated with pentobarbital sodium (30 mg/kg, intravenous injection) and ventilated with room air by a respirator (MAO01746, Harvard Apparatus Holliston, United States). Venous access was established to supply saline (50-100 mL/h) or pentobarbital sodium (2.5 mg/kg/h). Click to Show/Hide
Response Description	The exosome inhibitor GW4869 reduced ferroptosis, fibrosis, and inflammation and improved histological and electrophysiological remodeling. Pacing-CF-exos highly expressed miR-23a-3p by informatics analysis and experimental verification. Inhibitor- miR-23a-3p protected h9c2 cells from ferroptosis accompanying with upregulation of SLC7A11. The development of atrial fibrillation (AF) in a persistent direction could be prevented by intervening with exosomal miRNAs to reduce oxidative stress injury and ferroptosis.

RNA-binding motif, single-stranded-interacting protein 1 (RBMS1)

Regulator Info

Nortriptyline hydrochloride [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[6]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Doxorubicin (Dox)- inducible RBMS1 knockdown stable cells (3 x 10⁶ ) were injected subcutaneously into the abdomen side of 6-week-old BALB/c nude mice (Vital River). Mice were fed either with sucrose water or sucrose water containing 0.1% doxycycline hyclate. H1299 vector, 4 H1299 pLKO.1 RBMS1 and H1299 pLKO.1 RBMS1/SLC7A11 cells (2.5 x 10⁶ ) were injected subcutaneously into the abdomen side of 6-week-old BALB/c nude mice(Vital River). The xenograft tumour formation was monitored using callipers every 3 days. Click to Show/Hide
Response Description	RBMS1 ablation inhibited the translation of SLC7A11, reduced SLC7A11-mediated cystine uptake, and promoted ferroptosis. Nortriptyline hydrochloride decreased the level of RBMS1, thereby promoting ferroptosis. Importantly, RBMS1 depletion or inhibition by nortriptyline hydrochloride sensitized radioresistant lung cancer cells to radiotherapy.

RAF proto-oncogene serine/threonine-protein kinase (RAF1)

Regulator Info

Tetraarsenic tetrasulfide [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[7]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	MAPK signaling pathway			hsa04010
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	NCI-H23 cells	Lung adenocarcinoma	Homo sapiens	CVCL_1547
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	H1650-ER1 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_4V01
Response Description	On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in antiKRAS mutant lung cancer.

Protein FAM98A (FAM98A)

Regulator Info

Metformin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[8]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	RKO cells	Colon carcinoma	Homo sapiens	CVCL_0504
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
	LoVo cells	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	Caco-2 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0025
	HCT 15 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0292
	DLD-1 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	FHC cells	Normal	Homo sapiens	CVCL_3688
In Vivo Model	A total 1 x 10⁶ SW620-vector or SW620-FAM98A cells were suspended in 100 ul PBS and injected s.c. into the back of 4- to 6-week-old male BALB/cnude mice (Laboratory Animal Unit, Southern Medical University, China). The sizes of the resulting tumors were measured weekly. Tumor volumes were calculated as follows: total tumor volume (mm³) = (Length x Width2)/2, where Length is the longest length. When the tumor sizes reached about 200 mm³, nude mice in the four groups were given PBS or 5-FU treatment (30 mg/kg, intraperitoneal injection, twice a week), respectively. Nude mice were maintained in a barrier facility in racks filtered with a high-efficiency particulate air filter. Click to Show/Hide
Response Description	The expressions of FAM98A and SLC7A11 were also downregulated after metformin treatment. And FAM98A is predominantly expressed in the colorectal cancer tissues and high FAM98A expression is usually accompanied by the high expression of SLC7A11, which usually means ferroptosis resistance.

NF-kappa-B inhibitor alpha (NFKBIA)

Regulator Info

RSL3 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[9]
Regulator for Ferroptosis	Driver
Responsed Disease	Glioblastoma [ICD-11: 2A00]			Disease Info
Pathway Response	NF-kappa B signaling pathway			hsa04064
	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
In Vivo Model	Female B-NDG mice (4-6 weeks old, 16-20 g) were purchased from Biocytogen (Biocytogen Jiangsu Co., Ltd., Jiangsu, China) and housed under specific pathogen-free conditions. 5 x 10⁶ U87 cells were resuspended in 200 uL PBS buffer and then inoculated into the left hind limb of each mouse. Once tumor volumes reached >=50 mm³, the mice were randomly divided into four groups (n = 5): the control, RSL3-only, BAY-only, and RSL3 plus BAY groups. Chemicals were administered through intratumor injection (100 mg/kg for RSL3 and 1 mg/kg for BAY 11-7082) biweekly for two weeks. Click to Show/Hide
Response Description	NF-kB pathway activation is vital for RSL3-induced ferroptosis in glioblastoma cells both in vitro and in vivo. Furthermore, RNAi-mediated GPX4 silencing cannot trigger ferroptosis in glioblastoma cells unless the NF-kB pathway is activated simultaneously. Finally, NF-kB pathway activation promotes ferroptosis by downregulating the expression of ATF4 and SLC7A11.

NAD-dependent protein deacetylase sirtuin-1 (SIRT1)

Regulator Info

Quercetin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[10]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Status epilepticus [ICD-11: 8A66]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Male C57BL/6J mice (6-8 weeks of age, weighing 18-22 g) were obtained from Gempharmatech Co., Ltd (Changzhou, China). All mice were housed in cages with standard laboratory conditions: a consistent temperature of 24 , a 12 h light/dark cycle, and free access to water and food. The mice were randomized into four groups: 1) the KA group (n = 6), injected intraperitoneally with 20 mg/kg KA, as described in a previous study; while 2) the control group (n = 6), injected intraperitoneally with an equal volume of PBS; 3) the KA + QCT group (n = 6): this group was givenintragastric administrationof 50 mg/kg of QCT once daily for 21 days before KA injection based on the literature; and 4) the KA+ferrostatin1 (Fer-1) group (n = 6), injected intraperitoneally with a well-known ferroptosis inhibitor (3 mg/kg Fer-1) for 21 days before KA administration, as described in a previous study. Click to Show/Hide
Response Description	The association between the Nrf2-mediated ferroptosis pathway and seizures in a clinical setting. Quercetin effectively protects against seizure-induced neuron death in vivo and in vitro and alleviates cognitive function impairment via the SIRT1/Nrf2/SLC7A11/GPX4 pathway.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1)

Regulator Info

Micafungin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[11]
Regulator for Ferroptosis	Driver
Responsed Disease	Ischemia/reperfusion injury [ICD-11: DB98]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	The surgical procedure for establishing the myocardial I/R injury rat model was carried out as we did before. Briefly, a left thoracotomy was performed in the fourth intercostal space and the heart was exposed via opening thepericardium. The left coronary artery was surrounded with a 4-0 silk suture and a snare was formed by passing both ends of the suture via a short polyethylene tubing. Blockage of the coronary artery was conducted via clamping the snare against the heart surface. Reperfusion was performed by release of the snare. The sham group conducted the same procedure but without ischemia (the snare was not tightened). To establish the I/R injury model, the rat hearts were subjected to 1 h-ischemia plus 3 h-reperfusion. At the end, the blood and hearts were collected for assay of the creatine kinase(CK) activity and infarct size to determine the success of I/R injury model. To explore the role of MALT1 in myocardial I/R injury the underlying mechanisms, three sets of experiment were performed. Click to Show/Hide
Response Description	The inhibition of MALT1 can reduce ischemia/reperfusion-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway; and MALT1 may be used as a potential target to seek novel or existing drugs (such as micafungin) for treating myocardial infarction.

Mothers against decapentaplegic homolog 3 (SMAD3)

Regulator Info

Formononetin [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[12]
Regulator for Ferroptosis	Driver
Responsed Disease	Chronic kidney disease [ICD-11: GB61]	Disease Info
Pathway Response	Ferroptosis	hsa04216
	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mPRTECs (Mouse primary renal tubular epithelial cells)
In Vivo Model	For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium(30 mg/kg). Then, UUO surgery orsham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10% DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10% DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium (30 mg/kg). Then, UUO surgery or sham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10 % DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10 % DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. Click to Show/Hide
Response Description	Formononetin (FN) alleviates chronic kidney disease (CKD) by impeding ferroptosis-associated fibrosis by suppressing the Smad3/ATF3/SLC7A11 signaling and could serve as a candidate therapeutic drug for CKD. In addition, FN also promoted the separation of the Nrf2/Keap1 complex and enhanced Nrf2 nuclear accumulation.

Mitogen-activated protein kinase 8 (MAPK8)

Regulator Info

Seratrodast [Discontinued in Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[13]
Regulator for Ferroptosis	Driver
Responsed Disease	Status epilepticus [ICD-11: 8A66]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated. Click to Show/Hide
Response Description	Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures.

Mitogen-activated protein kinase 1 (MAPK1)

Regulator Info

Simvastatin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[14]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Corpus uteri cancer [ICD-11: 2C76]			Disease Info
Pathway Response	MAPK signaling pathway			hsa04010
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Ishikawa cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
Response Description	Simvastatin has the potential to be a targeted drug for endometrial cancer (EC) treatment. Besides, the inhibition to the RAS/MAPK signaling pathway allows simvastatin to induce ferroptosis through up-regulating the level of ROS, MDA, Fe2+, and TRF1 (TF) and reducing the level of GSH, SLC7A11, and FPN in cells.

LINC00618 (IncRNA)

Regulator Info

Vincristine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[15]
Regulator for Ferroptosis	Driver
Responsed Disease	Myeloid leukaemia [ICD-11: 2B33]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
Response Description	LINC00618, is reduced in human leukemia and strongly increased by vincristine (VCR) treatment. Furthermore, LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11).

Krueppel-like factor 4 (KLF4)

Regulator Info

Polyphyllin III [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[16]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Breast cancer [ICD-11: 2C60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Hs-578T cells	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
	HBL-100 cells	Normal	Homo sapiens	CVCL_4362
	BT-549 cells	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MDA-MB-453 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0418
In Vivo Model	MDA-MB-231 xenografts were established in 5 week-old BALB/C nude mice (Shanghai SLAC Laboratory Animal Corporation) by inoculating 1 x 10⁶ cells mixed with Matrigel (BD Biosciences) at a 1:1 ratio into the abdominal mammary fat pad. When the tumor reached 50-100 mm³, the mice were assigned randomly into different treatment groups (DMSO, PPIII, SAS, and PPIII + SAS groups), and each group consisted of 5 mice. PPIII (5 mg/kg/day) and SAS (200 mg/kg/day) were dissolved in dimethyl sulfoxide (DMSO), diluted in PBS, and then intraperitoneally injected into mice at a dose of 10 ml/kg/d once a day. Click to Show/Hide
Response Description	Polyphyllin III, which is a major saponin extracted fromParis polyphyllarhizomes, exerted its proliferation-inhibitory effect on MDA-MB-231 triple-negative breast cancer cells mainly through ACSL4-mediated lipid peroxidation elevation and ferroptosis induction. Polyphyllin III treatment also induced KLF4-mediated protective upregulation of xCT(SLC7A11), which is the negative regulator of ferroptosis.

Krueppel-like factor 15 (KLF15)

Regulator Info

Elabela [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[17]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Cardiomyopathy [ICD-11: BC43]	Disease Info
Pathway Response	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	rAFs (Rat adventitial fibroblasts)
Response Description	KLF15 siRNA impeded the beneficial roles of elabela (ELA) in DOX-pretreated rat aortic AFs by suppressing the Nrf2/SLC7A11/GPX4 signaling. In conclusion, ELA prevents DOX-triggered promotion of cytotoxicity, and exerts anti-oxidative and anti-ferroptotic effects in rat aortic AFs via activation of the KLF15/GPX4 signaling, indicating a promising therapeutic value of ELA in antagonizing DOX-mediated cardiovascular abnormality and disorders.

hsa-miR-489-3p (miRNA)

Regulator Info

Levobupivacaine [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[18]
Regulator for Ferroptosis	Driver
Responsed Disease	Gastric cancer [ICD-11: 2B72]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	GES-1 cells	Normal	Homo sapiens	CVCL_EQ22
	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
	SGC-7901 cells	Gastric carcinoma	Homo sapiens	CVCL_0520
In Vivo Model	Ten SCID nude mice aged 6-8 weeks were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China), and subcutaneously injected with SGC7901 cells (5 x 10⁶ cells per mouse) in left back. One week after feeding, the mice were randomly divided into two groups, the control and treatment group. For the next 25 days, the mice in treatment group were injected with erastin (15 mg/kg intraperitoneally) or co-treated with 40 mol/kg body weight of levobupivacaine once a day. The body weight and tumor size were measured every 3 days. Click to Show/Hide
Response Description	Levobupivacaine-upregulated miR-489-3p enhanced ferroptosis of gastric cancer cells by targeting SLC7A11. MiR-489-3p was involved in levobupivacaine-induced ferroptosis of gastric cancer cells. Levobupivacaine/miR-489-3p/SLC7A11 axis attenuates gastric cancer cell proliferationin vitro.

hsa-miR-382-5p (miRNA)

Regulator Info

Lidocaine [Investigative]

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[19]
Regulator for Ferroptosis	Driver
Responsed Disease	Breast cancer [ICD-11: 2C60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
In Vivo Model	SPF-level male nude mice aged 56weeks and weighted around 20 g were purchased from Vitalriver (China). All mice were maintained in a 12-hour circadian rhythm, and had free access to water and food. Cancer cells were subcutaneously injected into the right flank of mice. Lidocaine was administrated to mice at a dose of 1.5 mg per kg injected through the vail tails. For control group, the mice were treated with saline. Tumor volume and mice body weight were monitored every 5 days. Click to Show/Hide
Response Description	The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells.
Experiment 2 Reporting the Ferroptosis-centered Drug Response of This Regulator				[19]
Regulator for Ferroptosis	Driver
Responsed Disease	Ovarian cancer [ICD-11: 2C73]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	T-47D cells	Invasive breast carcinoma	Homo sapiens	CVCL_0553
In Vivo Model	SPF-level male nude mice aged 56weeks and weighted around 20 g were purchased from Vitalriver (China). All mice were maintained in a 12-hour circadian rhythm, and had free access to water and food. Cancer cells were subcutaneously injected into the right flank of mice. Lidocaine was administrated to mice at a dose of 1.5 mg per kg injected through the vail tails. For control group, the mice were treated with saline. Tumor volume and mice body weight were monitored every 5 days. Click to Show/Hide
Response Description	The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells.

hsa-miR-122-5p (miRNA)

Regulator Info

Isorhynchophylline [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[20]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Intracerebral hemorrhage [ICD-11: 8B00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	p53 signaling pathway			hsa04115
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection). Click to Show/Hide
Response Description	Isorhynchophylline (IRN) decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. In conclusion, IRN protects neurocyte from intracerebral hemorrhage (ICH)-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH.

Gap junction alpha-1 protein (GJA1)

Regulator Info

GAP 27 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[21]
Regulator for Ferroptosis	Driver
Responsed Disease	Acute kidney failure [ICD-11: GB60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Glutathione metabolism			hsa00480
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
In Vivo Model	Thirty-two male C57BL/6 mice (20 ± 2) g (Beijing Weitonglihua Experimental Animal Technology Co., Ltd.) were bred in individually ventilated cages (IVC) at SPF conditions, kept on a 12 h light/dark cycle, relative humidity conditions (40-70%) and controlled temperature (24 ± 2 ). After one-week acclimation mice were divided randomly into four groups: control group, cisplatin group (20 mg/kg cisplatin dissolved in saline), cisplatin + Fer-1 group (5 mg/kg Fer-1 dissolved in DMSO), and cisplatin + gap27 group (35 ug/kg gap27 dissolved in DMSO). There were eight animals in each group and 20 mg/kg cisplatin was given to each animal once by intraperitoneal injection except mice in the control group. Fer-1 and gap27 was administered 1 h before the injection of cisplatin. Click to Show/Hide
Response Description	Downregulation of Cx43 expression by gap27 reduced acute kidney injury in the animal model by inhibiting cisplatin-induced ferroptosis. Therefore, our results indicated that downregulation of Cx43 can inhibit ferroptosis by restoring the level of SLC7A11 in the system xctransporter and alleviate cisplatin-induced acute kidney injury.

Endothelial PAS domain-containing protein 1 (EPAS1)

Regulator Info

D-Mannose [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[22]
Regulator for Ferroptosis	Driver
Responsed Disease	Degenerative arthritis [ICD-11: FA05]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hCDs (Chondrocytes)
In Vivo Model	C57BL/6 J mice (8 weeks old, female) were purchased from Dossy Experimental Animal Limited Company (Chengdu, China). For surgery, mice were anaesthetized with pentobarbital sodium (100 mg/kg, injected intraperitoneally) and subjected to unilateral ACLT procedures. 28 The sham group received a skin incision and suturing without patellar dislocation or ligament transection. For virus injection, mice were intraarticularly injected with 1 x 10⁹ pfu (8 ul) of mock or AdEpas1 virus after one week of surgery. For Fer1 (MCE, Monmouth Junction, HY100579) injection, mice were intraarticularly injected with 1 mg/kg Fer1 or with vehicle two weeks after surgery, the injection was repeated once a week. Click to Show/Hide
Response Description	D-mannose alleviates osteoarthritis (OA) progression by suppressing HIF-2a-mediated chondrocyte sensitivity to ferroptosis. Overexpression of HIF-2a in chondrocytes by Ad- Epas1 intra-articular injection abolished the chondroprotective effect of D-mannose during OA progression and eliminated the role of D-mannose as a ferroptosis suppressor. Also, the RNA and protein levels of the two key ferroptosis suppressors, Gpx4 and Slc7a11, were increased in Dmannosetreated chondrocytes.

Cyclic GMP-AMP synthase (CGAS)

Regulator Info

Niraparib [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[23]
Regulator for Ferroptosis	Driver
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Cytosolic DNA-sensing pathway			hsa04623
Cell Process	Cell ferroptosis
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
	MC-38 cells	Colon adenocarcinoma	Homo sapiens	CVCL_B288
In Vivo Model	Six-week-old male BALB/c athymic nude mice were purchased from the Experimental Animal Center of Peking (Beijing, China). Stable cells (5 x 10⁶) were seeded into the right flanks of the mice. After the xenografts had grown to 200 mm³, saline as a vehicle or sorafenib (30 mg/kg) was administered by gavage every day, and the mice were euthanized by the cervical dislocation method five weeks later. Before sacrifice, the tumor sizes and body weights were measured twice per week. The tumor volume (V) was calculated as follows: (L x W2)/2 (length, L, and width, W). The xenografts were excised and further assessed. Click to Show/Hide
Response Description	Niraparib, a widely used PARPi, augmented cGAS-mediated ferroptosis and immune activation. In colorectal cancer models, cGAS signaling exerts tumor control via ATF3SLC7A11GPX4-mediated ferroptosis and IFNCD8 T cell-mediated antitumor immune response.

Cyclic AMP-dependent transcription factor ATF-3 (ATF3)

Regulator Info

Brucine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[24]
Regulator for Ferroptosis	Driver
Responsed Disease	Glioblastoma [ICD-11: 2A00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	U118 cells	Astrocytoma	Homo sapiens	CVCL_0633
	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
	A-172 cells	Glioblastoma	Homo sapiens	CVCL_0131
In Vivo Model	The athymic BALB/c nude mice (4 weeks; 20-22 g; Beijing Vital River Laboratory Animal Technology Company, China) were housed in a specific pathogen-free environment under a 12-h lightdark cycle with free access to food and water. The animals were allowed to acclimatize to their surroundings for 3 days. U87 cells (1 x 10⁶) in the logarithmic growth phase in 100 uL PBS were subcutaneously injected into the right flank. Therapeutic experiments were started when the tumor reached around 150 mm³ after about 10 days. Mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 6) or 40 mg/kg bodyweight (n = 6) in the same volume (50 uL) once a day for 13 times. Click to Show/Hide
Response Description	Brucine inhibited glioma cell growth in vitro and in vivo, and brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT (SLC7A11) to prevent H2O2 degradation on the other hand.

Formononetin [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[12]
Regulator for Ferroptosis	Driver
Responsed Disease	Chronic kidney disease [ICD-11: GB61]	Disease Info
Pathway Response	Ferroptosis	hsa04216
	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mPRTECs (Mouse primary renal tubular epithelial cells)
In Vivo Model	For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium(30 mg/kg). Then, UUO surgery orsham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10% DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10% DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. For UUO-induced CKD, the mice were randomly assigned into four groups (n = 6 per group): UUO, UUO + FN, UUO + VST, and Sham. The mice were anesthetized by intraperitoneal injection of pentobarbital sodium (30 mg/kg). Then, UUO surgery or sham operation was performed as previously described. Mice in the UUO + FN group were orally administrated with 40 mg/kg/day FN (dissolved in 10 % DMSO). For positive control, mice in UUO + VST group were orally treated with 20 mg/kg/day VST (dissolved in 10 % DMSO). Mice in the UUO and Sham groups were given equivalent solvent by oral. All mice were sacrificed 7 days post-UUO. Click to Show/Hide
Response Description	Formononetin (FN) alleviates chronic kidney disease (CKD) by impeding ferroptosis-associated fibrosis by suppressing the Smad3/ATF3/SLC7A11 signaling and could serve as a candidate therapeutic drug for CKD. In addition, FN also promoted the separation of the Nrf2/Keap1 complex and enhanced Nrf2 nuclear accumulation.

Cellular tumor antigen p53 (TP53)

Regulator Info

Pseudolaric acid B [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[25]
Regulator for Ferroptosis	Driver
Responsed Disease	Glioblastoma [ICD-11: 2A00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	U-87MG cells	Glioblastoma	Homo sapiens	CVCL_0022
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
	SHG-44 cells	Astrocytoma	Homo sapiens	CVCL_6728
In Vivo Model	Twenty athymic BALB/c nude mice (aged 4 weeks, weight 20-22 g, from Shanghai laboratory animal Center, Shanghai, China) were housed in a specific pathogen-free environment. A total of 1 x 10⁶ logarithmically growing C6 cells in 100 uL of PBS were subcutaneously injected into the right flank of each mouse. Therapeutic experiments were started when the tumor reached about 150 mm³ after about 7 days. The mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 5/group), PAB at the dosage of 10 mg/kg body weight (n = 10/group) and 20 mg/kg body weight (n = 10/group) in the same volume 50 uL once a days for 8 times. Click to Show/Hide
Response Description	Pseudolaric acid B (PAB) improved intracellular iron by upregulation of transferrin receptor. The increased iron activated Nox4, which resulted in overproduction of H2O2and lipid peroxides. Moreover, PAB depleted intracellular GSH via p53-mediated xCT (SLC7A11) pathway, which further exacerbated accumulation of H2O2and lipid peroxides. Thus, PAB triggers ferroptosis in glioma cells and is a potential medicine for glioma treatment.

Kayadiol [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[26]
Regulator for Ferroptosis	Driver
Responsed Disease	T-cell lymphoma [ICD-11: 2B01]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	YT cells	Natural killer cell lymphoblastic leukemia	Homo sapiens	CVCL_1797
	hPBLs (Human peripheral blood lymphocytes)
Response Description	Kayadiol decreased the expression of SLC7A11 and GPX4, the negative regulatory proteins for ferroptosis. And p53 was the key mediator of kayadiol-induced ferroptosis by SLC7A11/GPX4 axis through p53 knockout experiments. Kayadiol can serve as an effective alternative in the treatment of NK/T cell lymphoma.

Bavachin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[4]
Regulator for Ferroptosis	Driver
Responsed Disease	Osteosarcoma [ICD-11: 2B51]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MG-63 cells	Osteosarcoma	Homo sapiens	CVCL_0426
In Vitro Model	HOS cells	Osteosarcoma	Homo sapiens	CVCL_0312
Response Description	Bavachin could induce Osteosarcoma cell ferroptosis. Furthermore, bavachin elevated intracellular ferrous iron levels by increasing TFRC and DMT1 expression and decreasing FTH and FTL expressions. Bavachin also reduced SLC7A11 and GPX4 expression and promoted ROS and MDA accumulation by downregulating p-STAT3 to upregulate P53 expression.

Tanshinone IIA [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[27]
Regulator for Ferroptosis	Driver
Responsed Disease	Gastric cancer [ICD-11: 2B72]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	BGC-823 cells	Gastric carcinoma	Homo sapiens	CVCL_3360
	NCI-N87 cells	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_1603
In Vivo Model	All mice were housed under a setting of 12-h light/dark cycle at 22 ± 1, 55% humidity and fed with water and food provided at regular time. During the entire maintenance period, all mice were permitted free cage activity without joint immobilization. The initial body weights of the mice were between 20 and 23 grams. After subcutaneous injection of 2 x 10⁶ BGC-823 gastric cancer cells into the back of NOD-SCID mice, the mice were treated with or without Tan IIA (50 mg/kg) or Tan IIA in combination with Fer-1 (50 mg/kg). Tan IIA was diluted in DMSO:Methanol:Hydroxypropyl-b-cydodextrin (HP-b-CD) = 1:1:1. Fer-1 was also dissolved in DMSO:Methanol:HP-b-CD. Seven days after BGC-823 gastric cancer cells injection, intraperitoneal injection with Tan IIA was carried out every other day followed by killing at day 22 of tumor cell inoculation. All mice were killed by dislocation of the cervical vertebrae. Before killing, the tumor volume was measured every 3 days. All experiments were carried out using six mice each group in three independent experiments of a time-dependent manner with three time points. Click to Show/Hide
Response Description	Tanshinone IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT (SLC7A11) expression. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis.

Gambogenic Acid [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[28]
Regulator for Ferroptosis	Driver
Responsed Disease	Melanoma [ICD-11: 2C30]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Cell adhesion molecules			hsa04514
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	A-375 cells	Amelanotic melanoma	Homo sapiens	CVCL_0132
	A2058 cells	Amelanotic melanoma	Homo sapiens	CVCL_1059
Response Description	Gambogenic acid (GNA) significantly inhibited the invasion, migration and EMT in melanoma cells, and these cells exhibited small mitochondrial wrinkling (an important feature of ferroptosis). GNA upregulated the expression of p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the model cells, contributing to the mechanisms underlying GNA-induced ferroptosis.

Cyperquat [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[29]
Regulator for Ferroptosis	Driver
Responsed Disease	Parkinson disease [ICD-11: 8A00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC12 cells	Adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481
Response Description	As a classic drug employed inin vitromodels of Parkinson's disease, 1-methyl-4-phenylpyridinium (MPP) can induce senescence in PC12 cells. The expression of the ferroptosis-related proteins ASCL4 was upregulated and FTH1 was downregulated, which promoted accumulation of lipid peroxides and eventually led to ferroptosis. By rescuing MPP-induced ferroptosis, cell senescence could be inhibited, and its molecular mechanism was related to a p53/SLC7A11/GPX4 signaling pathway.

Seratrodast [Discontinued in Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[13]
Regulator for Ferroptosis	Driver
Responsed Disease	Status epilepticus [ICD-11: 8A66]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Drugs were dissolved in vehicle (0.1% DMSO + 20% PEG 300 + 0.5% CMC-Na + ddH2O). Mice in Control and PTZ groups were administered for five days with an equivalent volume of vehicle. PTZ-induced seizure model was done for the subsequent 1 h after the last administration of drugs. We performed a preliminary doseresponse trial, the dose of 60 mg/kg was established as being sufficient to trigger seizures with lower mortality and chosen as the optimal dose. One mouse in PTZ group was dead due to a severe seizure. At the end of the experiment, the mice were anesthetized or euthanized. For histopathological studies, the mice were anesthetized and intracardially perfused with 0.9% saline, followed by 0.4% paraformaldehyde for fixation of the brain. For immunoblot analysis, the hippocampus was rapidly isolated. Click to Show/Hide
Response Description	Seratrodast could reduce lipid ROS production, regulate the system xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis, and inhibit JNK (MAPK8) phosphorylation and p53 expression. JNK can directly or indirectly modulate the expression and activation of p53, which could regulate ferroptosis through inhibition of SLC7A11 transcription. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures in Epilepsy.

Isorhynchophylline [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[20]
Regulator for Ferroptosis	Driver
Responsed Disease	Intracerebral hemorrhage [ICD-11: 8B00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	p53 signaling pathway			hsa04115
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection). Click to Show/Hide
Response Description	Isorhynchophylline (IRN) decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. In conclusion, IRN protects neurocyte from intracerebral hemorrhage (ICH)-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH.

Ferric citrate [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[30]
Regulator for Ferroptosis	Driver
Responsed Disease	Sarcopenia [ICD-11: FB32]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Glutathione metabolism			hsa00480
Cell Process	Cell ferroptosis
In Vitro Model	C2C12 cells	Normal	Mus musculus	CVCL_0188
In Vivo Model	The 8-week- and 40-week-old male SAMP8 mice were purchased from the model animal research center of Zhishan Institute of Healthcare Research Co., Ltd. (Beijing, China). All the mice were kept in an SPF grade animal facility at 24 with a relative humidity of 50%-60%, and in a light/dark cycle of 12 h/12 h. Click to Show/Hide
Response Description	Ferric citrate induced ferroptosis in C2C12 cells, as well as impaired their differentiation from myoblasts to myotubes. Iron overload upregulated the expression of P53, which subsequently repressed the protein level of Slc7a11 (solute carrier family 7, member 11), a known ferroptosis-related gene. Targeting iron accumulation and ferroptosis might be a therapeutic strategy for treating sarcopenia.

CD44 antigen (CD44)

Regulator Info

Sodium butyrate [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[31]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	FHC cells	Normal	Homo sapiens	CVCL_3688
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
In Vivo Model	Six-week-old male C57BL/6J mice were purchased from the Medical Laboratory Animal Center of Guangdong Province (Foshan, China). Forty-five C57BL/6L mice were randomized into 4 groups after 1 week of adaptive feeding: (1) Control group (n = 9); (2) AOM/DSS group (n = 12); (3) AOM/DSS + NaB (orally) group (n = 12); 4) AOM/DSS + NaB (intraperitoneal injection) group (n = 12). The Control group received an intraperitoneal injection of saline solution beginning on day 1, and received sterile drinking water throughout the study. Other three groups received an intraperitoneal injection of 10 mg/kg AOM (Sigma Aldrich) beginning on day 1, and received drinking water containing 2.5% DSS at the second and eighth weeks (2% DSS in the fifth week). Besides, 0.1 M NaB (Sigma Aldrich) was given in drinking water during the whole experiment process in AOM/DSS + NaB (p.o.) group, while AOM/DSS + NaB (i.p.) group was injected intraperitoneally (IP) with 1 g/kg NaB per day. Click to Show/Hide
Response Description	Sodium butyrate (NaB) induces ferroptosis in colorectal cancer cells through the CD44/SLC7A11 signaling pathway and has synergistic effects with Erastin.

Bromodomain-containing protein 4 (BRD4)

Regulator Info

JQ1 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[32]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Breast cancer [ICD-11: 2C60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell autophagy
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	Hs-578T cells	Invasive breast carcinoma	Homo sapiens	CVCL_0332
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	MCF-10A cells	Normal	Homo sapiens	CVCL_0598
In Vivo Model	Female athymic BALB/c nude mice (4-6-week old) were obtained from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Approximately 1 x 10⁷ cells (A549) in 200 uL of serum-free medium and Matrigel solution were injected directly into the right axilla of each mouse. Tumor growth was measured with calipers every 3 days. Click to Show/Hide
Response Description	Ferroptosis was induced under (+)-JQ1 treatment and BRD4 knockdown, indicating that (+)-JQ1 induces ferroptosis via BRD4 inhibition in breast adenocarcinoma. In addition, expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under (+)-JQ1 treatment. Moreover, JQ1 treatment and BRD4 knockdown led to decreased FTH1 expression.

5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)

Regulator Info

Sulfasalazine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[33]
Regulator for Ferroptosis	Driver
Responsed Disease	Colon cancer [ICD-11: 2B90]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
Cell Process	Cell autophagy
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	Calu-1 cells	Lung squamous cell carcinoma	Homo sapiens	CVCL_0608
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	To generate murine subcutaneous tumors, 5 x 10⁶ HCT116, CX-1, or HT1080 cells in 100 ul phosphate buffered saline (PBS; Thermo Fisher Scientific, AM9625) were injected subcutaneously right of the dorsal midline in athymic nude immunodeficient mice (six- to eight-week-old, female). To generate orthotopic tumors, 1 x 10⁶ KPC cells in 10 ul PBS were surgically implanted into the pancreases of immunocompetent C57BL/6J mice (six- to eight-week-old, female). Click to Show/Hide
Response Description	BECN1 plays a novel role in lipid peroxidation that could be exploited to improve anticancer therapy by the induction of ferroptosis. Mechanistically, phosphorylation of BECN1 at Ser90/93/96 by PRKAA/ AMPK contributes to the formation of a BECN1-SLC7A11 complex and system Xc-inhibition. Knockdown of BECN1 by shRNA inhibits ferroptosis induced by system X-c- inhibitors (e.g., erastin, sulfasalazine, and sorafenib) in Colon carcinoma.

5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)

Regulator Info

Fingolimod [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[34]
Regulator for Ferroptosis	Driver
Responsed Disease	Multiple myeloma [ICD-11: 2A83]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	AMPK signaling pathway			hsa04152
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	U266B1 cells	Plasma cell myeloma	Homo sapiens	CVCL_0566
	RPMI-8226 cells	Plasma cell myeloma	Homo sapiens	CVCL_0014
Response Description	Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Fingolimod (FTY720) can activate PP2A subunit C and dephosphorylate AMPKa, and then inhibit the expression of SLC7A11 and GPX4. In conclusion, FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway.

Unspecific Regulator

Indole-3-pyruvic acid [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[105]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	MLL/AF4+ RS4 cells	Adult B acute lymphoblastic leukemia	Homo sapiens	CVCL_0093
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
	NIH3T3 cells	Normal	Mus musculus	CVCL_0594
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
Response Description	Indole-3-pyruvate (I3P) suppresses ferroptosis by direct free radical scavenging and through the activation of an anti-oxidative gene expression program in Childhood acute monocytic leukemia. And I3P elevated the activation of compensatory gene expression as indicated by increased protein amounts of SLC7A11 and HO-1, two important target genes of anti-oxidative stress pathways.

Imidazole ketone erastin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[106]
Responsed Disease	Diffuse large B-cell lymphoma [ICD-11: 2A81]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	SU-DHL-1 cells	Anaplastic large cell lymphoma	Homo sapiens	CVCL_0538
	SU-DHL-2 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_9550
	SU-DHL-6 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_2206
	SU-DHL-8 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_2207
	SU-DHL-10 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1889
	SU-DHL-16 cells	B-cell non-Hodgkin lymphoma	Homo sapiens	CVCL_1890
	A3/Kawakami cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1062
	OCI-LY8 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_8803
	U-937 cells	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
	DoHH2 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1179
	HBL-1 cells	Non-Hodgkin lymphoma	Homo sapiens	CVCL_M572
	U-2932 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1896
	SU-DHL-7 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_4380
	SU-DHL-9 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_4379
	A4/Fukuda cells	B acute lymphoblastic leukemia	Homo sapiens	CVCL_1064
	WSU-NHL cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1793
	SU-DHL-5 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1735
	Karpas-422 cells	Diffuse large B-cell lymphoma	Homo sapiens	CVCL_1325
In Vivo Model	NOD/SCID mice (12-weeks of age and ~28 g weight) were weighed before injection and divided into groups of 3 mice per cage. Mice were dosed using three different routes, IP and PO with 50 mg/kg IKE, and IV with 17 mg/kg IKE. Samples were collected at 0, 1, 3, 4, and 8 h from three mice per time point. Additionally, three mice per group were used as controls by administration with equivalent amount of vehicle 1 by IP, PO, and IV, and samples were collected at 8 h. At the appropriate time, mice were sacrificed by CO2 asphyxiation for 3 min and ~0.5 mL of blood was collected via cardiac puncture. Click to Show/Hide
Response Description	Imidazole ketone erastin (IKE) is a potent, selective, and metabolically stable system xc- (SLC7A11)inhibitor. In addition, biodegradable polyethylene glycol-poly(lactic-co-glycolic acid) nanoparticles were employed to aid in IKE delivery and exhibited reduced toxicity compared with free IKE in a diffuse large B cell lymphoma (DLBCL) xenograft model.

Tirapazamine [Phase 3]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[107]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
In Vitro Model	143B cells	Osteosarcoma	Homo sapiens	CVCL_2270
	MNNG/HOS Cl #5 cells	Osteosarcoma	Homo sapiens	CVCL_0439
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
Response Description	SLC7A11 overexpression could restored the proliferation and migration abilities inhibited by Tirazamine. Thus, TPZ could inhibit the proliferation and migration of osteosarcoma cells, and induce ferroptosis in part through inhibiting SLC7A11.

Berberine [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[108]
Responsed Disease	Gastrointestinal cancer [ICD-11: 2B5B]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell autophagy
	Cell proliferation
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	TMK-1 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_4384
	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
In Vivo Model	Five-week-old male BALB/c mice were purchased from SLC Japan (Shizuoka, Japan). The animals were maintained in a pathogen-free animal facility under a 12 h light/dark cycle in a temperature (22 )- and humidity-controlled environment, in accordance with the institutional guidelines approved by the Committee for Animal Experimentation of Nara Medical University, Kashihara, Japan, following the current regulations and standards of the Japanese Ministry of Health, Labor and Welfare (approval no. 12924, 5 November 2020). Animals were acclimated to their housing for seven days before the start of the experiment. For the peritoneal dissemination tumor model, CT26 cancer cells (1 x 10⁷ in 0.2 mL per mouse) were injected into the mouse peritoneal cavity. To measure tumor weight, mice were euthanized on Day 12 and the tumors were excised, while the peritoneal tumors were dissected from the intestine, mesenterium, diaphragm, and abdominal wall, with gross removal of non-tumor tissues. The largest tumor was formed on the diaphragm, and paraffin-embedded sections of the excised diaphragmatic tumor were prepared and stained with hematoxylin-eosin. BBR was diluted with distilled water to produce a final concentration of 48 mg/mL. The solutions were ultrasonically treated for 1 h, and fully vortexed for 30 min. BBR solution was administered by free drinking. The intake calculated from the amount of water consumed was 15.2 mg/kg body weight/day. Click to Show/Hide
Response Description	Berberine induces apoptosis and ferroptosis by inhibiting mitochondrial complex I and promoting autophagy, leading to combined cell death in the gastrointestinal cancer and suppressing stemness. BBR induces cell death in GIC cells accompanied by increased mitochondrial superoxide and ACSL4 levels, decreased SLC7A11, and impaired antioxidant mechanisms, indicated by decreased GPX4 expression and decreased GSH.

Atranorin [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[109]
Responsed Disease	Gastric cancer [ICD-11: 2B72]	Disease Info
Pathway Response	Ferroptosis	hsa04216
	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hGCCs (Gastric cancer cells)
In Vivo Model	NOD-scid mice (NOD.CB17-Prkdcscid/NcrCrl) aged 6-7 weeks and weighing 20-22 g were used in the experiment. The animal study was performed at the Shanghai University of Traditional Chinese Medicine with approval from the Institutional Animal Care and Use Committee in accordance with the institutional guidelines. All mice were randomly divided into two groups, and each group consisted of four mice. In experimental group, approximately 1 x 10⁵ GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul Atranorin@SPION (10 mg/kg) every 2 days. In control group, approximately 1 x 10⁵ GCSCs in logarithmic growth phase were harvested and inoculated subcutaneously into NOD-scid mice, and intraperitoneal injection of 100 ul SPION (10 mg/kg) alone every 2 days. After 2 months, the mice were sacrificed, and their tumors were excised. Click to Show/Hide
Response Description	Atranorin@SPIONs significantly reduced the 5-hydroxymethylcytidine modification level of GPX4 and SLC7A11 mRNA 3' untranslated region in gastric cancer cells. This study revealed the molecular biological mechanism by which Atranorin@SPION inhibit the in vitro and in vivo activity of GCSCs, that is, Atranorin@SPION reduced the expression of members of the Xc-/GPX4 axis and reduced their mRNA 5-hydroxymethylcytidine modification, finally induced ferroptosis of GCSCs.

Actinidia chinensis Planch [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[110]
Responsed Disease	Gastric cancer [ICD-11: 2B72]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
In Vitro Model	HGC-27 cells	Gastric carcinoma	Homo sapiens	CVCL_1279
In Vivo Model	Wild type AB strain of zebrafish (Danio rerio) was obtained from Southern Medical University. The HGC-27 cells labeled with EGFP were resuspended in PBS in the concentration of 5*10⁷/ml. 10 nl cell suspension containing approximately 300 cells were loaded into capillary needles and injected into the abdominal perivitelline space of zebrafish embryos by a nanoliter injector (Narishige, Tokyo, Japan). After injection, the tumor-bearing embryos were transferred into a 24-well plate and acclimated in embryo water at 35 for 24 h and then incubated at 0, 90, 180 mg/ml ACP decoction for 48 h. Click to Show/Hide
Response Description	Actinidia chinensis Planch (ACP) increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype.

Pt3R5G [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[111]
Responsed Disease	Colon cancer [ICD-11: 2B90]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	RKO cells	Colon carcinoma	Homo sapiens	CVCL_0504
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	NCM460 cells	Normal	Homo sapiens	CVCL_0460
In Vivo Model	Five-week-old male BALB/c-nude mice from Central Laboratory of Animal, Xi'an Jiaotong University Health Science Center were housed 4 per cage under controlled temperature (23 ± 2 ), a 12 h/12 h light/dark cycle with ad libitum access to food and water and specific pathogen-free conditions. Twelve BALB/c-nude mice were randomly divided into three groups (control, 25 mg/kg, 50 mg/kg). 1 x 10⁶ RKO cells were subcutaneously injected into either side of the same mice dorsal flanks. After 14 days, animals then received Pt3R5G (25 mg/kg, 50 mg/kg) byintraperitoneal injectionfor 15 days. The weight of mouse and tumor nodules sizer were measured every 3 days for 29 days. Click to Show/Hide
Response Description	Pt3R5G significantly down-regulated SLC7A11 expression and up-regulated TFR1 in RKO cells. Pt3R5G inhibits cell proliferation through inducing ferroptosis by down-regulating SLC7A11 in colon cancer.

Propofol [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[112]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
In Vitro Model	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
In Vivo Model	CT26 (1 x 10⁵ cells/100 uL) were injected into thetail veinof male BALB/c mice. Then the mice were randomly divided into saline, vehicle, propofol, and sevoflurane groups (n = 5 per group). Saline, fat emulsion (as vehicle control of propofol), and propofol (200 mg/kg) were intraperitoneally injected, while sevoflurane (1.8-2.0%) was administered by inhalation for 2 h. In another set of experiments, coloncancer cells (CT26 and HT29) were pretreated with two doses of propofol (5 ug/mL, 10 ug/mL) or fat emulsion (as vehicle control of propofol) in a cell culture medium for 2 h. After washing with phosphate-buffered saline (PBS), the cells were harvested,counted on a hemacytometer and prepared. Cells (CT26: 1 x 10⁵ cells/100 uL, HT29: 1 x 10⁶ cells/100 uL) were finnally injected into mice through the tail vein.Lung metastasiswas detected via hematoxylin and eosin staining (HE) or ex vivo bioluminescence imaging. Click to Show/Hide
Response Description	Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting colorectal cancer cell metastasis through Nrf2-mediated ferroptosis inhibition.

2-Imino-6-methoxy-2H-chromene-3-carbothioamide [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[113]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	mTOR signaling pathway			hsa04150
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	DLD-1 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
In Vivo Model	Five-week-old female BALB/c nude mice were purchased from Beijing Weitong Lihua Experimental Animal Technical Co., Ltd. (Beijing, China). The mice were randomly assigned to the treatment and control groups until the tumor size reached approximately 100 mm³. The mice in the treatment group were injected with 0.174 mg/mL IMCA (100 uL), and those in the control group were injected with an equal volume of normal saline. The nude mice were euthanized, and samples were obtained from their tumor, heart, hepar, kidney, and blood after 33 days of IMCA treatment. Click to Show/Hide
Response Description	2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) significantly induced the ferroptosis of colorectal cancer cells. Mechanistically, IMCA downregulated the expression of SLC7A11 and decreased the contents of cysteine and glutathione, which resulted in reactive oxygen species accumulation and ferroptosis.

Talaroconvolutin A [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[114]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	5 x 10⁶ HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm³, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days. Click to Show/Hide
Response Description	Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy.

Sorafenib [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[115]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	SNU-182 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0090
	SNU-449 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_0454
In Vivo Model	A total of 20 male Balb/c nude mice aged 6-8 weeks were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China). Five million Huh7 cells were inoculated into the right flanks of the mice. When the tumor size reached 80-100 mm³, the mice were randomly divided into four groups and administered artesunate (30 mg/kg mouse weight) alone, sorafenib (20 mg/kg mouse weight) alone, a combination of artesunate and sorafenib, or the same volume of PBS by gavage every other day. Click to Show/Hide
Response Description	Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in hepatocellular carcinoma treatment.

Necrostatin-1 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[116]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
	SK-HEP-1 cells	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens	CVCL_0525
Response Description	Necrostatin-1 potentiated sulfasalazine-induced expression of SLC7A11, a catalytic subunit of system xc- in these cells. And necrostatin-1 Prevents Ferroptosis in a RIPK1- and IDO-Independent Manner in Hepatocellular Carcinoma.

Ginkgetin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[117]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	SPC-A1 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In Vivo Model	Briefly, when tumours on transplanted nude mice reached around 100 mm³, the mice were randomized divided into eight groups: control, ginkgetin, DDP, ginkgetin + DDP, UAMC 3203, ginkgetin + UAMC 3203, DDP + UAMC 3203, ginkgetin + DDP + UAMC 3203. Both DDP (3 mg/kg) and ginkgetin (30 mg/kg) were administered by intraperitoneal injection, with 2 - 3 times per week and once per day, respectively. UAMC 3203 (10 mg/kg) was administered 5 days/week by intraperitoneally injection. Tumour size and body weight were measured 3 times per week. After dosing 31 days, the nude mice were sacrificed, and tumours were removed and weighed. Click to Show/Hide
Response Description	The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured non-small cell lung cancer (NSCLC) cells.

Sulforaphane [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[118]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Glutathione metabolism			hsa00480
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	H69 cells	Normal	Homo sapiens	CVCL_8121
	NCI-H82 cells	Lung small cell carcinoma	Homo sapiens	CVCL_1591
	H69AR cells	Lung small cell carcinoma	Homo sapiens	CVCL_3513
Response Description	Sulforaphane (SFN)-induced cell death was mediated via ferroptosis and inhibition of the mRNA and protein expression levels of SLC7A11 in small-cell lung cancer (SCLC) cells. The anticancer effects of SFN may provide novel options for SCLC treatment.

Capsaicin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[119]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vitro Model	NCI-H23 cells	Lung adenocarcinoma	Homo sapiens	CVCL_1547
Response Description	Capsaicin inhibited the proliferation of A549 and NCI-H23 cells and induced ferroptosis by inactivating SLC7A11/GPX4 signaling. Capsaicin could be used as a potential anticancer agent in the treatment of non-small cell lung cancer.

Manoalide [Phase 2]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[120]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	H157 cells	Oral cavity Squamous cell carcinoma	Homo sapiens	CVCL_2458
	HCC827 cells	Lung adenocarcinoma	Homo sapiens	CVCL_2063
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
In Vivo Model	The LSL-KrasG12D mouse model was obtained from the Jackson Laboratory (Sacramento, CA). Adeno-Cre (Genechem, Shanghai, China) was introduced into the trachea of mice at a dose of 1.25 x 10₁₁ PFU in a total volume of 50 uL. Tumor tissues from 12-week post-infection mice were washed with cold PBS, cut into small pieces, and washed with DMEM/F12 (containing 1 x Glutamine, 10 mM HEPES, and antibiotics), digested with collagenase I and IV for 0.5-1 h at 37. After washing twice with DMEM/F12 and centrifugation (500 g, 5 min), the dissociated cells were seeded into growth factor-reduced matrigel (Corning, #356237) at 37 for 30 min. Click to Show/Hide
Response Description	Manoalide (MA) induces ferroptosis by suppressing the NRF2-SLC7A11 axis and mitochondrial Ca2+overload induced-FTH1 pathways to promote the sensitivity of osimertinib-resistant lung cancer cells to osimertinib.

XAV939 [Preclinical]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[121]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
In Vitro Model	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
Response Description	The downregulation of the lncRNA MIR503HG induced by XAV939 may serve an important role in suppressing the progression of non-small cell lung cancer via sponging miR1273c, to downregulate its target SOX4. Furthermore, the downregulation of SLC7A11 induced by XAV939 may inhibit NSCLC development via participation in the ferroptosis pathway.

Sulfasalazine [Investigative]

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[122]
Responsed Disease	Breast cancer [ICD-11: 2C60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
Response Description	The combined effects of vorinostat with salazosulfapyridine (SASP) depend on the accumulation of ROS caused by a decrease in intracellular GSH levels, possibly due to SASP-mediated inhibition of xCT. xCT (coded by the SLC7A11 gene), a light chain subunit of the glutamate-cystine antiporter system Xc(-) in Breast adenocarcinoma.
Experiment 2 Reporting the Ferroptosis-centered Drug Response of This Regulator				[123]
Responsed Disease	Uterine serous carcinoma [ICD-11: 2C72]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	hUPSCs (Human uterine serous papillary carcinoma-1 cells)
	Abcam HeLa ERGIC2 KO cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_B1RG
	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In Vivo Model	The mean weight of the mice at the start was 19.4 ± 0.87 g. To generate the subcutaneous xenograft model, USPC1 (5 x 10⁶ cells) or PTX1 (5 x 10⁶ cells) were suspended in 200 ul of PBS following determination of cellular viability and injected into the subcutaneous tissue of 6-week-old female Crj:SHO-PrkdcscidHrhr hairless SCID mice (n = 2) (Charles River Laboratories Inc.). Tumor formation was visually confirmed in mice inoculated with USPC1 cells, but not in those inoculated with PTX1 cells, thus the animal study was performed using USPC1 cells. The recipient mice were monitored for general health status and presence of subcutaneous tumors once a week. Click to Show/Hide
Response Description	The effect of the xCT (SLC7A11) inhibitor, sulfasalazine on cytotoxicity was stronger in paclitaxel-resistant uterine serous carcinoma (USC) cells compared with that in paclitaxel-sensitive USC cells. Furthermore, the synthetic lethal interaction between the accumulation of ROS and the activation of the Ras effector, JNK, induced cell-proliferation inhibition and ferroptotic cell death in paclitaxel-resistant USC cells.

Norcantharidin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[124]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
In Vitro Model	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
In Vivo Model	Athymic nu/nu female mice aged 6-8 weeks (n = 9; mean weight, 20.21 ± 1.54 g) were purchased from the specific pathogen SPF (Beijing) Lab Animals Technology Co. Ltd. Mice were housed in a temperature- and humidity-controlled environment (20-24 , 45-55% humidity), with free access to food and water and in groups of three. All procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC ID: 17-3256) at Nantong University and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. Click to Show/Hide
Response Description	Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following norcantharidin (NCTD) treatment. Collectively, NCTD may represent a potent anticancer agent in ovarian cancer cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/HO-1/GPX4/xCT axis.

Cryptochlorogenic acid [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[125]
Responsed Disease	Diabetes mellitus [ICD-11: 5A10]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	INS-1 cells	Insulinoma	Rattus norvegicus	CVCL_0352
In Vivo Model	Sixty Sprague-Dawley (SD) rats with weights ranging from 250-270 g were obtained from experimental animal center of Xiamen university. For diabetes model group, fasting was performed for 12 h before experiment. The rats (ten rats per group) were assigned into Control group, Model (DM) treated with 50 mg/kg streptozotocin (STZ) via abdominal injection, positive control group and experimental groups. The blood glucose level, which is served as the indicator for the diabetes, was monitored herein. The glucose level after modeling is above 16.7 mmol/l, supporting that the modeling is successful. Click to Show/Hide
Response Description	Cryptochlorogenic acid (CCA) functions via inhibition of ferroptosis by activation of cystine/glutamate transporter system (XC)/glutathione peroxidase 4(GPX4)/Nrf2 and inhibition of nuclear receptor coactivator 4 (NCOA4) in diabetes. System xc- which is composed of SLC7A11 and SLC3A2, served as the provider of GSH synthesis.

N-acetylcysteine [Approved]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[126]
Responsed Disease	Ovarian dysfunction [ICD-11: 5A80]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
	Cell differentiation
In Vitro Model	hPTs (Human placental tissues)
In Vivo Model	Adult Sprague-Dawley rats (70 days old) of both sexes were purchased from the Laboratory Animal Centre of Harbin Medical University, Harbin, China. Before the experiment, female rats were allowed to acclimatize for a minimum of 1 week and then were monitored daily by vaginal lavage to determine the stage of the estrous cycle as previously described (Zhanget al., 2016). Pregnancy was achieved by housing female rats on the night of proestrus with fertile males of the same strain at a 2:1 ratio. Confirmation of mating was performed the morning after by the presence of a vaginal plug, and this was considered as GD 0.5. The rats were sacrificed between 8:00 a.m. and 9:00 a.m. hours on GD 14.5. Click to Show/Hide
Response Description	Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical polycystic ovary syndrome (PCOS)-like rat model. N-acetylcysteine treatment results in increased mRNA expression of Aifm2, a negative regulator of GPX4-independent ferroptosis in the placenta. Moreover, NAC reverses HAIR-induced uterine and placental ferroptosis through activation of the Slc7a11/GSH/GPX4 axis.

Liraglutide [Approved]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[127]
Responsed Disease	Cognitive disorder [ICD-11: 6D71]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mHNs (Mouse hippocampal neurons)
In Vivo Model	Male diabetic db/db mice and nondiabetic littermate db/m mice that were 4 weeks of age were purchased from Changzhou Cavens Experimental Animal Co., Ltd. After 1week of adaptive feeding, 20 db/db mice were randomly divided into two groups: a model group (db/db, n = 10) and a treatment group (LIRA, n = 10). Another 10 db/m mice were used as the control group (db/m, n = 10). After feeding to 10weeks old, the LIRA group was given liraglutide (CSN11311, CSNpharm, China) diluent (200 ug/kg/d) by intraperitoneal injection for 5 weeks, with equivoluminal 0.9% saline intraperitoneally administered to the other two groups. Click to Show/Hide
Response Description	Liraglutide was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetes-induced cognitive dysfunction and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.

Paraquat [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[128]
Responsed Disease	Parkinson disease [ICD-11: 8A00]			Disease Info
Pathway Response	Apoptosis			hsa04210
	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell apoptosis
In Vitro Model	SH-SY5Y cells	Neuroblastoma	Homo sapiens	CVCL_0019
In Vivo Model	Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments. Click to Show/Hide
Response Description	Paraquat (PQ) significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of Parkinson's disease occurrence.

Baicalin [Terminated]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[129]
Responsed Disease	Intracerebral hemorrhage [ICD-11: 8B00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC12 cells	Adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481
In Vivo Model	A total of 60 male C57BL/6 mice (10weeks old, 25-28g) were purchased from Guangzhou University of Chinese Medicine Experimental Animal Center (Guangzhou, China). The mice were maintained with enough food and water at 24, 60% relative humidity and 12/12h light/dark cycle. The mice were randomly divided into three groups: sham operation group (Sham), ICH model group (Mod) and baicalin group (Bai) (n = 20/group). Baicalin was suspended in 0.5% carboxymethylcellulose sodium solution. Given the extremely low solubility of baicalin, the concentration of baicalin solution was 0.5 mg/ml. To achieve 20 mg/kg/day dosage, the baicalin solution was administered to the mice in the Bai group by oral route twice at an interval of 1 h within 2 h after ICH injury onset. The remaining two groups received an equal volumes of saline through oral gavage. Since the second day after ICH, mice in the Bai group received 20 mg/kg of baicalin solution while those in the remaining two groups received equal volumes of saline once a day for three consecutive days. Click to Show/Hide
Response Description	Baicalin significantly increased the mRNA expression of GPX4 and SLC7A11 in the perihematoma brain tissues of intracerebral hemorrhage (ICH) model mice. Baicalin can inhibit the development of ferroptosis in ICH. Baicalin is a potential therapeutic drug for ICH treatment.

Galangin [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[130]
Responsed Disease	Cerebral ischemia [ICD-11: 8B10]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mHNs (Mouse hippocampal neurons)
In Vivo Model	Male gerbils weighing 70-90 g (12 weeks) were selected for this study. Gerbils were anesthetized with 7% chloral hydrate (350 mg/kg) and the bilateral common carotid arteries were occluded using artery clips. After 5 min, the clips were removed to restore cerebral blood flow. After the operation, place the gerbil on an electric blanket to keep the gerbil's body temperature. The sham group underwent the same surgical procedure without ligation of carotid arteries and was given an equal volume of physiological saline as in the treated groups. The model + galangin (Jiangsu Yongjian Pharmaceutical Technology, 548-83-4, Purity: >=98% (HPLC)) groups underwent the same procedure as the model group and then were received galangin at 25, 50, or 100 mg/kg/day for two continuous weeks. Click to Show/Hide
Response Description	Gerbils treated with galangin after ischemia-reperfusion (I/R) injury showed significant improvements in learning and memory. In addition, galangin treatment reduced the levels of lipid peroxide in the brains of gerbils that underwent I/R as well as reduced the amount of cell death and increased the expression of SLC7A11 and glutathione peroxidase 4 (GPX4).

Chrysin [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[131]
Responsed Disease	Cerebral ischemia [ICD-11: 8B10]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups (200, 100, and 50 mg/kg), and a positive drug group (Ginaton, 21.6 mg/kg). The CIRI model was induced in rats by transient middle cerebral artery occlusion (tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. Click to Show/Hide
Response Description	The chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by cerebral ischemia-reperfusion injury.

Kaempferol [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[132]
Responsed Disease	Cerebral ischaemic stroke [ICD-11: 8B11]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	mPCNs (Mouse primary cortical neurons)
Response Description	Kaempferol provides protection from OGD/R-induced ferroptosis, at least in part, by activating Nrf2/SLC7A11/GPX4 signaling pathway. Therefore, pharmacological inhibition of ferroptosis may be an attractive therapeutic target for the treatment of ischemic stroke.

Canagliflozin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[133]
Responsed Disease	Cardiomyopathy [ICD-11: BC43]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Male C57BL/6J mice aged 6-8 weeks with weights of 18-20 g were obtained from the Slack Laboratory Animal Co., Ltd. (Shanghai, China). Mice were allowed to acclimatize in the laboratory environment for 1 week before the beginning of the experiment. DCM model establishment: The mice were given a single intraperitoneal injection of 150 mg/kg 1% streptozotocin (STZ, V900890, Sigma, USA, dissolved in 0.1 mol/L sodium citrate buffer, pH = 4.4 - 4.6). Mouse blood from the tail vein was collected in each group of the model mice and tested by glucose meter (Accu-Chek Performa test strips, Roche, Accu-Chek Performa Combo, Roche, USA) on day 3, 5 and 7 after injection. Click to Show/Hide
Response Description	Canagliflozin (Cana) promotes upregulation of SLC7A11 and downregulation of TfR1 and FTN-H, which protect the cardiomyocytes from ferroptosis. These finding suggests that Cana inhibit ferroptosis by balancing cardiac iron homeostasis and promoting the system Xc/GSH/GPX4 axis in diabetic cardiomyopathy.

Liquiritin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[134]
Responsed Disease	Cardiomyopathy [ICD-11: BC43]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	The set of animal experiments was designed to evaluate the effectiveness of liquiritin on doxorubicin-induced cardiotoxicity as were as ferroptosis were explored. Mice were randomly divided into 5 groups: (1) the control group; (2) doxorubicin group; (3) the doxorubicin plus liquiritin group (20 mg/kg); (4) the doxorubicin plus liquiritin group (40 mg/kg); (5) the doxorubicin plus liquiritin group (80 mg/kg) (Han et al.2022; Mou et al.2021). The control group and doxorubicin group were given equal volume of 0.5% sodium carboxymethylcellulose; the doxorubicin plus liquiritin groups were given different doses of liquiritin (0.5%) sodium carboxymethylcellulose co-suspension) by intragastric administration 7 days in advance once a daily. On day 8, groups (2), (3), (4), and (5) were given a single intraperitoneal injection of 15 mg/kg of DOX to establish a model of doxorubicin-induced cardiotoxicity; and group (1) was given an equal volume of saline intraperitoneally. Click to Show/Hide
Response Description	Liquiritin can protect the doxorubicin-induce mice's cardiotoxicity, and its beneficial effect is related to the reduction of ferroptosis through a mechanism involving the regulation of the SLC7A11/GPX4 pathway.

Atorvastatin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[135]
Responsed Disease	Congestive heart failure [ICD-11: BD10]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	8-week C57BL/6J male mice purchased from Comparative Medicine Center of Yangzhou University were retained with unrestricted access to sterilized diet and water at standard bio-clean laboratory settings (Experimental Animal Center of College of Veterinary Medicine of Yangzhou University). Animals were randomly divided into four groups(n = 6-8 mice per group): control group or ISO group: injected with saline or ISO (5 mg/kg) subcutaneously for 14 days and, meanwhile, received vehicle saline via gavage for 14 days respectively; ATV (Pfizer,USA) group or ISO + ATV group: injected with saline or 5 mg/kg ISO (Sigma, USA) subcutaneously for 14 days and, meanwhile, received 20 mg/kg ATV via gavage for 14 days respectively. Click to Show/Hide
Response Description	Atorvastatin showed significantly protective effects through suppressing the activation of ferroptosis related signaling, as evidenced by decreasing the mRNA levels of PTGS2 (a marker of ferroptosis), contents of malonaldehyde and protein levels of NOX4 and increasing the contents of glutathione (GSH), the ratio of GSH/GSSG and protein levels of GPX4 and SLC7A11. ATV reduced cardiac hypertrophy and fibrosis and accumulation of iron in heart failure.

Astragaloside IV [Investigative]

In total 2 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[136]
Responsed Disease	Cardiovascular diseases [ICD-11: BE2Z]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	HUVECs (Human umbilical vein endothelial cells)
Response Description	Astragaloside IV partially upregulated the levels of SLC7A11 and GPX4 expression which were reduced by LPC. The LPC-suppressed proliferation and LPC-induced apoptosis and senescence of endothelial cells were greatly attenuated by AS-IV treatment. In conclusion, AS-IV could serve as a novel drug for treating ferroptosis-related cardiovascular diseases.
Experiment 2 Reporting the Ferroptosis-centered Drug Response of This Regulator		[142]
Responsed Disease	Lung injury [ICD-11: NB32]	Disease Info
Pathway Response	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hT2AECs (Type II alveolar epithelial cells)
In Vivo Model	The animals were randomly assigned to six groups (7 mice in each) as follows: (I) Normal saline (NS) group, (II) Ast-IV 100 mg/kg (Ast) group, (III) PM2.5 group, (IV) Ast-IV 50 mg/kg + PM2.5 (Ast-L) group, (V) Ast 100 mg/kg + PM2.5 (Ast-H) group, and (VI) Ast-IV 100 mg/kg + erastin 20 mg/kg + PM2.5 (Era) group. Based on our previous results, this study adopted anintraperitoneal injection(i.p.) of Ast-IV (dissolved in normal saline containing 0.1% DMSO for preventive treatment. After all the mice were adaptively fed for 5 days, in the NS and PM2.5 groups, mice received the normal saline containing 0.1% DMSO viai.p.once a day for the next three consecutive days. Similar to the NS group, in the Ast, Ast-H, and Era groups, mice received Ast-IV (100 mg/kg) viai.p. Ast-L group received Ast-IV (50 mg/kg) viai.p. To evaluate the effect of Ast-IV on ferroptosis in PM2.5-induced lung injury, we used the ferroptosis agonist erastin to activate ferroptosisin vivo. In the Era group, mice received erastin (20 mg/kg, 10% DMSO + 40% PEG300 + 5%Tween80 + 45% normal saline) 30 min before each preventive treatment of Ast-IV. Click to Show/Hide
Response Description	Astragaloside IV (Ast-IV) reduced the lung wet-dry ratio and the levels of interleukin 6 (IL-6), tumor necrosis factor- (TNF-) and interleukin 1 (IL-1) in serum. Ast-IV could also improve the oxidative stress level in BALF, restore the GSH level in the lung tissue, and reduce the iron content in the lung tissue. Western blot outcomes revealed that Ast-IV regulated the ferroptosis signaling pathway via the Nrf2/SLC7A11/GPX4 axis to protect PM2.5-mediated lung injury.

Sesamin [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[137]
Responsed Disease	Cardiovascular diseases [ICD-11: BE2Z]	Disease Info
Pathway Response	Fatty acid metabolism	hsa01212
	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	rHTs (Rat hippocampal tissues)
In Vivo Model	Forty specific pathogen-free normal Sprague Dawley (SD) rats (7 weeks old and 251-275 g in weight) were supplied by Charles River Laboratories. The SD rats were randomly allocated into five groups (n = 8). In the PM2.5 exposure group, the rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. In the saline control group, the SD rats were treated with 0.5% CMC (10 mL per kg b.w.) for 21 days. The SD rats were anesthetized with isoflurane and intratracheally instilled with 0.9% saline (1 mL per kg b.w.) every other day for a total of three times. In the Ses pretreatment groups, the SD rats were gavaged with low (L-Ses, 40 mg per kg b.w), medium (M-Ses, 80 mg per kg b.w.), and high (H-Ses, 160 mg per kg b.w.) doses of Ses. The SD rats were anesthetized with isoflurane and administered with PM2.5 suspension by intratracheal instillation (10 mg per kg b.w.) every other day for a total of three times. Click to Show/Hide
Response Description	Sesamin pretreatment upregulated the expression levels of GPX4, SLC7A11, TFRC, and FPN1 and inhibited the expression levels of FTH1 and FTL. Ses pretreatment could ameliorate PM2.5-induced cardiovascular injuries perhaps by inhibiting ferroptosis.

Chrysophanol [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[138]
Responsed Disease	Liver fibrosis [ICD-11: DB93]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HSC-T6 cells	Normal	Rattus norvegicus	CVCL_0315
Response Description	Chrysophanol significantly induced HBx-transfected HSC-T6 death by inducing ferroptosis, as demonstrated by lipid ROS accumulation and upregulation of expression of ER markers, such as Bip, CHOP, and p-IRE1, and ferroptotic markers, such as GPX4 and SLC7A11. Therefore, chrysophanol may exert ferroptotic effects on activated HSCs to prevent liver fibrosis.

Salidroside [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[139]
Responsed Disease	Ischemia/reperfusion injury [ICD-11: DB98]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
In Vivo Model	Following endotracheal intubation, mice were ventilated with room air at a rate of 120 cycles/min and atidal volumeof 7 mL/kg (MiniVent, Harvard Apparatus, USA). To induce ischemia, mice underwent left thoracotomy, and the left pulmonary hilum was blocked for 60 min with a microvascular clamp. After ischemia, the coronary artery was reperfused for 120 min by removing the clamp. The mice were euthanized at the end of the experiment through CO2 asphyxiation and cervical dislocation. Next, bronchoalveolar lavage fluid (BALF), blood, and lung samples were collected for testing. Click to Show/Hide
Response Description	Salidroside postconditioning attenuates ferroptosis-mediated lung ischemia-reperfusion injury by activating the Nrf2/SLC7A11 signaling axis.

Dimethyl fumarate [Approved]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[140]
Responsed Disease	Ischemia/reperfusion injury [ICD-11: DB98]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	AML12 cells	Normal	Mus musculus	CVCL_0140
In Vivo Model	The mice were randomly divided into four groups of six: sham + vehicle, sham + DMF, IR + vehicle, and IR + DMF. The mice were supplemented with DMF at a concentration of 100 mg/kg or DMSO by daily oral gavage for a week before surgery, as previously reported. As stated in a prior study, the partial warm liver IRI model was developed. Briefly, the sham group only had free hepatic portal blood vessels after laparotomy, and the blood flow was not obstructed. As for the hepatic IR group, the blood supply to the left and mid-hepatic lobes was blocked, resulting in 70% mouse liver IRI for 90 min. The mice were put on a heated blanket after surgery in order to maintain body temperature and monitor vital signs. Blood supply was restored for 6 h. Died mice were eliminated for testing prior to sample collection. The mice were euthanized after the sample were obtained. The same experimenter carried out all surgeries. Click to Show/Hide
Response Description	NRF2 knockdown notably decreased the expression of SLC7A11 and HO-1 and blocked the anti-ferroptosis effects of dimethyl fumarate (DMF). DMF inhibits ferroptosis by activating the NRF2/SLC7A11/HO-1 axis and exerts a protective effect against hepatic ischemia-reperfusion injury.

Aspirin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[141]
Responsed Disease	Chronic kidney disease [ICD-11: GB61]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
In Vivo Model	These mice were on eight weeks old male DBA/2J background (n = 36, HFK Bioscience, Beijing, China). They were randomized one of the six groups: control normal mice group (NC); diabetic mice group (DM); diabetic mice group (Fer-1), who intraperitoneal injected Fer-1 (Selleck, Houston, TX, USA); diabetic mice group (vehicle-P), who intraperitoneal injected 1% dimethyl sulfoxide (DMSO); diabetic mice group (As), who intragastric administrated Aspirin (Solarbio, Beijing, China); diabetic mice group (vehicle-G), who intragastric administrated 0.5% sodium carboxymethyl cellulose (Na-CMC; Solarbio, Beijing, China). Diabetes models were induced with 5 consecutive days of a single intraperitoneal injection of streptozotocin 40 mg/kg (dissolved in 0.1 M citrate buffer, pH 4.5; SigmaAldrich, St Louis, MO, USA). Control mice only was injected the same volume of citrate buffer. In the Fer-1 or vehicle-P groups, the diabetic mice were treated respectively with Fer-1 (2.5 umol/kg, dissolved in 1% DMSO) or 1% DMSO during the duration of treatment for 12-week every day. And in the AS and vehicle-G groups, the diabetic mice were treated respectively with aspirin (50 mg/kg, dissolved in 0.5% Na-CMC) or 0.5% Na-CMC for 12-week every day. Click to Show/Hide
Response Description	Aspirin can upregulate SLC7A11 and GPX4 expression by suppressing COX2. Our results demonstrated that ferroptosis in renal tubular cells contributes to Diabetic kidney disease (DKD) development and that diabetes-related ferroptosis was inhibited through the downregulation of COX2 by aspirin, thus retarding the progression of DKD.

Lipopolysaccharide [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[143]
Responsed Disease	Lung injury [ICD-11: NB32]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
In Vivo Model	The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. Click to Show/Hide
Response Description	The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues.

Ferrostatin-1 [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[143]
Responsed Disease	Lung injury [ICD-11: NB32]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
In Vivo Model	The male C57BL/6 mice were divided randomly into 4 groups (n = 4 per group, 8-10 weeks old, weight = 23-25 g): the control group receiving 0.9% NaCl (containing 0.1% DMSO), the LPS group receiving LPS plus 0.9% NaCl (containing 0.1% DMSO), the Fer-1 group receiving Fer-1 only, and the LPS + Fer-1 group receiving both Fer-1 and LPS. The LPS-induced ALI model was induced by instilling intratracheally 50 ul of LPS solution (0.2 g/L), then Fer-1 (0.8 mg/kg) was administered after LPS challenge via tail vein injection. The Fer-1 was dissolved in DMSO first, and diluted with 0.9% NaCl. The final concentration of Fer-1 and DMSO was 0.2 mg/ml and 0.1% respectively. Click to Show/Hide
Response Description	The cell viability of BEAS-2B was down-regulated by lipopolysaccharide (LPS) treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by ferrostatin-1. Fer-1 exerted therapeutic action against LPS-induced acute lung injury, and down-regulated the ferroptosis level in lung tissues.

Lycopene [Investigative]

In total 1 item(s) under this drug		Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator		[144]
Responsed Disease	Injury of intra-abdominal organs [ICD-11: NB91]	Disease Info
Pathway Response	Ferroptosis	hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mSCs (Mouse splenocytes)
In Vivo Model	Three-week-old specific pathogen-free ICR (Institute of Cancer Research) male mice (weights of 18-22 g) were provided by Liaoning Changsheng Biotech Co. Ltd. The mice were housed under conditions at 22 ± 2 with 35-65% humidity and a light/dark cycle of 12 h/12 h in the cage. The animals were quarantined for a week before formal experiments, then randomly divided into seven groups: vehicle control group (Vcon), control group (Con), 5 mg/kg BW/d Lyc group (Lyc), 500 and 1000 mg/kg BW/d DEHP group (D5 and D10, respectively), DEHP + Lyc group (DL5 and DL10, respectively) (n = 20). The animals were exposed to DEHP via oral gavage, which lasted for 28 d, and then sacrificed after being anesthetized. Click to Show/Hide
Response Description	DEHP disrupted the GSH metabolism via the xc/ GPX4 antioxidant system and, subsequently, caused the ferroptotic cell death, but Lycopene (Lyc) could effectively mitigate DEHP-induced damage to the antioxidant system. These findings indicated that Lyc may be an effective strategy for the prevention of DEHP-induced splenic toxicity via the regulation of ferroptosis.

T-2 Toxin [Investigative]

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[146]
Responsed Disease	Health [ICD-11: N.A.]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vitro Model	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
Response Description	SLC7A11 overexpression significantly rescued the enhanced ferroptosis caused by T-2 toxin. T-2 toxin induces ferroptosis by downregulating SLC7A11 expression. Ferroptosis mediates T-2 toxin-induced cytotoxicity by increasing ROS and downregulating SLC7A11 expression.

References

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Prof. Shuiping Liu