Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10520)

Regulator Name	Cellular tumor antigen p53 (TP53)
Synonyms	P53; Antigen NY-CO-13; Phosphoprotein p53; Tumor suppressor p53 Click to Show/Hide
Gene Name	TP53
Gene ID	7157
Regulator Type	Protein coding
Uniprot ID	P04637
Sequence	MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP DEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNS SCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELP PGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG GSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD Click to Show/Hide
Family	p53 family
Function	Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2. However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Click to Show/Hide
HGNC ID	HGNC:11998
KEGG ID	hsa:7157

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

TP53 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).

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Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]

Target Info

In total 5 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[1]
Target for Ferroptosis	Suppressor
Responsed Disease	Oral squamous cell carcinoma		ICD-11: 2B6E	Disease Info
Responsed Drug	Quisinostat		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Necroptosis			hsa04217
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
	Cell pyroptosis
In Vitro Model	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
	Tca8113 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
In Vivo Model	Adult male athymic BALB/c nude mice (20-22 g of 5-week-old mice) were housed in a controlled environment at 23 ± 2 and 40%-70% humidity under a 12 h dark/light cycle with free access to irradiated food and sterile water. A suspension of 6 x 10⁶/100 uL TCA-8113 cells was inoculated subcutaneously into the hind flank region of each nude mouse. The average tumor volume in nude mice reached 100 mm³, and mice were randomly divided into three groups. Quisinostat was formulated in normal saline and administered at 3 and 10 mg/kg/day byintraperitoneal injection. Control mice were given equal volume saline intraperitoneally. The tumor volume and the bodyweight of mice were monitored every three days. Click to Show/Hide
Response regulation	Quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.
Experiment 2 Reporting the Ferroptosis Target of This Regulator				[2]
Target for Ferroptosis	Suppressor
Responsed Disease	Status epilepticus		ICD-11: 8A66	Disease Info
Responsed Drug	Apigenin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	SH-SY5Y cells	Neuroblastoma	Homo sapiens	CVCL_0019
In Vivo Model	5-weeks-old kainate (KA)-induced BALB/c nude mice, a widely used epilepsy mouse model, were performed with intraperitoneal (i.p.) injection of KA (6 mg/kg). Pre-treatment 21 with antioxidant apigenin (60 mg/Kg, 2 days) or post-treatment with apigenin (60 mg/Kg, 1 day), mice were injected with KA (6 mg/kg) via intraperitoneal (i.p.) injection, and then HCP (0.5 mg/Kg) were injected by intravenous (i.v.) injection. In vivo and Ex vivo fluorescence images of relative ClO levels in mice brains 5, 15, 30, 45, and 60 min post injection of HCP were further performed by using the IVIS Spectrum imaging system (Nanjing University) with an excitation filter of 430 nm and the collection wavelength range is from 500-600 nm. Click to Show/Hide
Response regulation	Apigenin can efficiently reduce the expression of intracellular MPO and increase the levels of GPX4 and SIRT1, thereby conferring neuroprotection through regulation of kainic acid (KA)-induced ferroptosis. And the level of Ac-p53 inside the brains treated with apigenin was down-regulated, suggesting that the p53-mediated ferroptosis pathway might be blocked. Overall, apigenin was screened and confirmed as an efficient lead compound for epilepsy prevention and treatment.
Experiment 3 Reporting the Ferroptosis Target of This Regulator				[30]
Target for Ferroptosis	Suppressor
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ubiquitin mediated proteolysis			hsa04120
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	HIEC-6 cells	Normal	Homo sapiens	CVCL_6C21
Response regulation	RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4 in colon carcinoma cells, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis.
Experiment 4 Reporting the Ferroptosis Target of This Regulator				[31]
Target for Ferroptosis	Suppressor
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	Ferroptosis			hsa04216
	MAPK signaling pathway			hsa04010
	Fatty acid metabolism			hsa01212
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
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Six 4-week-old male BALB/c nude mice were ordered from the Shanghai Laboratory Animal Center (Shanghai SLAC Laboratory Animal Co., Ltd., China). A total of 5 x 10⁶ TIPE+/+ SW480 cells were suspended in 100 uL of PBS and subcutaneously injected into the right axilla flank of each nude mouse, and the same amount of vector SW480 cells was into the left. At 2 weeks after inoculation, the xenograft tumor size was measured using Vernier calipers every 2 days. Click to Show/Hide
Response regulation	MiR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. In addition, SAPK/JNK is the upstream molecule of p53. MiR-539 is a new therapeutic target for colorectal cancer (CRC) patients.
Experiment 5 Reporting the Ferroptosis Target of This Regulator				[32]
Target for Ferroptosis	Suppressor
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
Response regulation	Cold induction promotes the process of ferroptosis by inducing the expression of CIRBP and then regulating key factors such as p53 and GPX4[. In addition, cold induction significantly inhibited the proliferation of pancreatic cancer cells and induced cell apoptosis, but after the addition of ferroptosis inhibitor, cell proliferation and apoptosis did not change significantly.

Diamine acetyltransferase 1 (SAT1) [Driver]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator			[3]
Target for Ferroptosis	Driver
Responsed Disease	Neurotoxicity	ICD-11: NE61	Disease Info
Responsed Drug	Sevoflurane	Approved	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	Pregnant rats were placed in a dedicated plastic chamber with ambient gas at a flow rate of 2L/min. Fer-1 solubilized in saline and 1% dimethyl sulfoxide (DMSO) and PD146176 (a specific 15LOX inhibitor) dissolved in corn oil containing 1% DMSO were administered intraperitoneally to rats at a dose of 5 mg/kg 1 h before each exposure, respectively. Similarly, 0.5 mg/kg Ku55933 (an ATM inhibitor), which is diluted in saline containing 1% DMSO, was intraperitoneally administered 2 h previously. Click to Show/Hide
Response regulation	Sevoflurane could enhance 15LO2-PEBP1 interaction and activate ATM and its downstream P53/SAT1 pathway, which might be attributed to excessive p-ATM nuclear translocation, indicating a potential therapeutic target for ameliorating sevoflurane-induced neurotoxicity.

Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]

Target Info

In total 10 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[4]
Target for Ferroptosis	Suppressor
Responsed Disease	Glioblastoma		ICD-11: 2A00	Disease Info
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 regulation	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.
Experiment 2 Reporting the Ferroptosis Target of This Regulator				[5]
Target for Ferroptosis	Suppressor
Responsed Disease	T-cell lymphoma		ICD-11: 2B01	Disease Info
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 regulation	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.
Experiment 3 Reporting the Ferroptosis Target of This Regulator				[6]
Target for Ferroptosis	Suppressor
Responsed Disease	Osteosarcoma		ICD-11: 2B51	Disease Info
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
	HOS cells	Osteosarcoma	Homo sapiens	CVCL_0312
Response regulation	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.
Experiment 4 Reporting the Ferroptosis Target of This Regulator				[7]
Target for Ferroptosis	Suppressor
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
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 regulation	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.
Experiment 5 Reporting the Ferroptosis Target of This Regulator				[8]
Target for Ferroptosis	Suppressor
Responsed Disease	Melanoma		ICD-11: 2C30	Disease Info
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 regulation	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.
Experiment 6 Reporting the Ferroptosis Target of This Regulator				[9]
Target for Ferroptosis	Suppressor
Responsed Disease	Parkinson disease		ICD-11: 8A00	Disease Info
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 regulation	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.
Experiment 7 Reporting the Ferroptosis Target of This Regulator				[10]
Target for Ferroptosis	Suppressor
Responsed Disease	Status epilepticus		ICD-11: 8A66	Disease Info
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 regulation	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.
Experiment 8 Reporting the Ferroptosis Target of This Regulator				[11]
Target for Ferroptosis	Suppressor
Responsed Disease	Intracerebral hemorrhage		ICD-11: 8B00	Disease Info
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 regulation	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.
Experiment 9 Reporting the Ferroptosis Target of This Regulator				[12]
Target for Ferroptosis	Suppressor
Responsed Disease	Sarcopenia		ICD-11: FB32	Disease Info
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 regulation	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.
Experiment 10 Reporting the Ferroptosis Target of This Regulator				[34]
Target for Ferroptosis	Suppressor
Responsed Disease	Lung injury		ICD-11: NB32	Disease Info
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 regulation	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.

Unspecific Target [Unspecific Target]

In total 30 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[13]
Responsed Disease	HIV Infection		ICD-11: 1C60	Disease Info
Responsed Drug	Methamphetamine		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
Response regulation	Methamphetamine (METH) and HIV-1 lead to oxidative stress and their combined effect increases the risk of HIV-associated neurocognitive disorder (HAND), which may be related to the synergistic ferroptotic impairment in microglia. We found that METH and HIV-1 Tat reduced the expression of ferroptotic protein GPX4 and the cell viability and enhanced the expression of P53 and the level of ferrous iron, while the above indices were significantly improved with pretreatment of ferrostatin-1.
Experiment 2 Reporting the Ferroptosis Target of This Regulator				[14]
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Responsed Drug	Albiziabioside A		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	hBMECs (Human brain microvascular endothelial cells)
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	HaCaT cells	Normal	Homo sapiens	CVCL_0038
	HCT-8 cells	Ileocecal adenocarcinoma	Homo sapiens	CVCL_2478
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	CCD-841CoN cells	Normal	Homo sapiens	CVCL_2871
	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
	BEL-7402 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
In Vivo Model	A total of 1 x 10⁷ HCT116 cells were subcutaneously inoculated into the right flank of BALB/c mice. When tumor reached 70-100 mm³ (10 days after implant), mice were divided into five groups of eight animals at random. The groups with D13 were administered intravenously 20 mg/kg and 10 mg/kg. The positive control group was treated with AlbA(20 mg/kg and 10 mg/kg) through intravenous injection. The negative control group received 0.9% normal saline through intravenous injection. Click to Show/Hide
Response regulation	The study synthesized a series of Albiziabioside A derivatives and evaluated the antitumor activity both in vitro and in vivo. Compound D13 could induce apoptosis and ferroptosis through the mitochondrial pathway as a p53 activator. In addition, compound D13 significantly suppressed tumorigenesis without inducing toxicity in normal organs in vivo. The antitumor efficacy of D13 was further verified in colon cancer xenograft mouse models.
Experiment 3 Reporting the Ferroptosis Target of This Regulator				[15]
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Responsed Drug	Ginkgo biflavones		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	RKO cells	Colon carcinoma	Homo sapiens	CVCL_0504
	LoVo cells	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	HCT-116 cells (5 x 10⁶) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately). Click to Show/Hide
Response regulation	Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.
Experiment 4 Reporting the Ferroptosis Target of This Regulator				[16]
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Responsed Drug	BEBT-908		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	MC-38 cells	Colon adenocarcinoma	Homo sapiens	CVCL_B288
In Vivo Model	About 2 x 10⁵ MC38 tumor cells were inoculated subcutaneously into C57BL/6 mice. A total of 100 mg/kg BEBT-908 was intravenously injected every other day for four times initiating from day 4 after tumor cell inoculation. Tumors were harvested on day 12 after inoculation, weighted, mechanically minced and incubated with 50 ug/mL DNase I (Sigma) and 2 mg/mL collagenase P (Sigma) for 20 minutes at 37. Click to Show/Hide
Response regulation	Treatment with BEBT-908 promoted ferroptotic cell death of cancer cells by hyperacetylating p53 and facilitating the expression of ferroptotic signaling. The dual PI3K/HDAC inhibitor BEBT-908 elicits potent antitumor responses, effectively inducing immunogenic ferroptosis of colorectal cancer cells and potentiating cancer immunotherapy.
Experiment 5 Reporting the Ferroptosis Target of This Regulator				[17]
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Responsed Drug	Dihydroartemisinin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
In Vivo Model	Six to eight-week-old female C57BL/6 mice were purchased from the Experimental Animal Center of Military Medical Sciences (Beijing, China). C57BL/6 mice were anesthetized and the tail of the pancreas was exposed. Panc 02 cells were resuspended in PBS at a concentration of 1 x 10⁶ cells/0.1 ml and 50 ul cells were injected into the tail of the pancreas. Tumor-bearing mice were randomly divided into two groups (3 days after implantation). The control group was intraperitoneally injected 200 ul PBS daily for 10 days, and the DHA group was intraperitoneally injected with 100 mg/kg DHA daily for 10 days. The pancreatic tumors and spleens of the mice were collected for subsequent analysis. Click to Show/Hide
Response regulation	Dihydroartemisinin has anti-tumor effect in pancreatic cancer cells in vitro and in vivo. DHA treatment induced ferroptosis by increasing P53 and AOLX12 expression.
Experiment 6 Reporting the Ferroptosis Target of This Regulator				[18]
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Responsed Drug	Levobupivacaine		Approved	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A427 cells	Lung carcinoma	Homo sapiens	CVCL_1055
In Vivo Model	Balb/c nude mice (n= 5, 4-week-old, male) were applied to detect the impact of levobupivacaine on tumor growth. Mice subcutaneously injected with 1 x 10⁷ A549 cells were treated with levobupivacaine (40 umol/Kg) or equal volume saline. The tumor volume was remarked every 5 days and finished at 30 days after injection, followed by the analysis of volume (length (width/2)2) and weight. Click to Show/Hide
Response regulation	Levobupivacaine could inhibit the proliferation and induce the apoptosis of non-small cell lung cancer (NSCLC) cells. Levobupivacaine was able to attenuate the invasion and migration in the cells. The treatment of levobupivacaine remarkably increased the levels of ROS, iron, and Fe2+ in NSCLC cells. Mechanically, levobupivacaine up-regulated the expression of p53 and induced ferroptosis by regulating p53 in NSCLC cells.
Experiment 7 Reporting the Ferroptosis Target of This Regulator				[19]
Responsed Disease	Ovarian cancer		ICD-11: 2C73	Disease Info
Responsed Drug	Apatinib		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
Response regulation	Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis.
Experiment 8 Reporting the Ferroptosis Target of This Regulator				[19]
Responsed Disease	Ovarian cancer		ICD-11: 2C73	Disease Info
Responsed Drug	Olaparib		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
Response regulation	Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis.
Experiment 9 Reporting the Ferroptosis Target of This Regulator				[20]
Responsed Disease	Prostate cancer		ICD-11: 2C82	Disease Info
Responsed Drug	Flubendazole		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145 cells	Prostate carcinoma	Homo sapiens	CVCL_0105
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	RWPE-1 cells	Normal	Homo sapiens	CVCL_3791
In Vivo Model	24 nude mice (3-4 weeks) were acquired from the experimental animal center of southern medical university (GuangZhou, China) and kept under specific pathogen-free conditions. 4 x 10⁶ PC3 cells were implanted subcutaneously into the right armpit regions of each nude mouse. When the tumors volume reached approximately 40 mm³, mice were randomly divided into two groups to receive flubendazole (10 mg/kg, once daily), 5-fluorouracil (30 mg/kg, once daily), their combination, and vehicle control by intraperitoneal injection. After 20 days of treatment, all mice were sacrificed and tumor weight and tumor volume were immediately measured, respectively. Click to Show/Hide
Response regulation	Flubendazole is a novel P53 inducer which exerts anti-proliferation and pro-apoptosis effects in castration-resistant prostate cancer (CRPC) through hindering the cell cycle and activating the ferroptosis, and indicates that a novel utilization of flubendazole in neoadjuvant chemotherapy of CRPC.
Experiment 10 Reporting the Ferroptosis Target of This Regulator				[21]
Responsed Disease	Hereditary Leiomyomatosis		ICD-11: 2C90	Disease Info
Responsed Drug	Artesunate		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Caki-1 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	786-O cells	Renal cell carcinoma	Homo sapiens	CVCL_1051
	KTCTL-26 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_5872
	A-498 cells	Renal cell carcinoma	Homo sapiens	CVCL_1056
Response regulation	Artesunate (ART) significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant renal cell carcinoma (RCC) cells. P53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.
Experiment 11 Reporting the Ferroptosis Target of This Regulator				[22]
Responsed Disease	Adrenocortical carcinoma		ICD-11: 2D11	Disease Info
Responsed Drug	Romidepsin		Investigative	Drug Info
Pathway Response	Cell adhesion molecules			hsa04514
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	SW13 cells	Adrenal cortex carcinoma	Homo sapiens	CVCL_0542
Response regulation	HDAC inhibitor Romidepsin converted SW13+ cells also had reduced mRNA expression of the mitochondrial ROS detoxifier superoxide dismutase 2 (SOD2), and the tumor suppressor p53. HDAC inhibitor treatment synergistically increased adrenocortical carcinoma cell death following induction of ferroptosis.
Experiment 12 Reporting the Ferroptosis Target of This Regulator				[23]
Responsed Disease	Parkinson disease		ICD-11: 8A00	Disease Info
Responsed Drug	Clioquinol		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	PI3K-Akt signaling pathway			hsa04151
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	SK-N-SH cells	Neuroblastoma	Homo sapiens	CVCL_0531
In Vivo Model	In total, twelve healthy adult rhesus monkeys (Macaca mulatta lasiotis, aged 4-5 years, and weighed 3.5-5 kg at the start of the study) were obtained from Sichuan Primed Biological Technology Co., Ltd. Monkeys were randomly divided into two groups: normal (control) group (n = 3) and MPTP group (n = 9). Monkeys from MPTP group were administered with MPTP by intramuscular injection daily at the beginning of the study, and then the MPTP dose was gradually added to 0.5 mg/kg at the end of the experiment. Monkeys from control group were injected with saline instead, and the other conditions were the same with MPTP group. Click to Show/Hide
Response regulation	Ferroptosis was probably involved in the pathogenesis of parkinson's disease (PD). Clioquinol (CQ) can decrease the excessive iron in the SN to normal level and directly protect DA neurons against oxidative stress probably by activating the AKT/mTOR survival pathway and blocking p53-medicated cell death.
Experiment 13 Reporting the Ferroptosis Target of This Regulator				[24]
Responsed Disease	Parkinson disease		ICD-11: 8A00	Disease Info
Responsed Drug	Ferric ammonium citrate		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	MES23.5 cells	Normal	Mus musculus	CVCL_J351
In Vivo Model	Human a-synuclein (a-Syn) A53T overexpressiontransgenic mice(B6; C3-Tg (Prnp-SNCA*A53T) 83Vle/J) were originally obtained in breeding pairs from the Jackson Laboratory (004479) to generate a stable breeding colony. Animals were raised according to SPF level, kept at constant temperature (20 ± 2) , constant humidity (50 ± 10%), day and night cycle light (12-12 h), with free access to food and water. Click to Show/Hide
Response regulation	Ferroptosis firstly occurred in a relatively low concentration of ferric ammonium citrate (FAC)-treated group, and then apoptosis appeared in response to the increased iron doses. This was also confirmed in vivo in parkinson's disease transgenic mice and the underlying mechanism might be associated with the p53 signaling pathway, but not MAPK signaling pathway.
Experiment 14 Reporting the Ferroptosis Target of This Regulator				[25]
Responsed Disease	Cardiomyopathy		ICD-11: BC43	Disease Info
Responsed Drug	Berberine		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	All animal experiment protocols were implemented in accordance with the National Institutes of Health (NIH) guidelines, and the procedures were approved by the Animal Ethics Committee of Southwest University. C57BL/6J male mice, 8-10 weeks old, weighing 20 ± 2 g, were used in this study. Mice were housed under standard conditions at 22-24 with a 12 h light/12 h darkness cycle and free access to food and tap water. Thirty-six mice were randomly divided into six groups: control (N = 8), IMA group (50 mg/kg) (N = 8), Low-Ber (20 mg/kg) + IMA group (N = 8), Medium-Ber (40 mg kg1) + IMA group (N = 8), High-Ber (80 mg/kg) + IMA group (N = 8), and Fer-1 (1 mg/kg) + IMA group (N = 8). IMA was given intraperitoneally for 14 days. Ber was given orally 2 h before IMA treatment and Fer-1 was given intraperitoneally 2 h before IMA treatment. Click to Show/Hide
Response regulation	Berberine downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against IMA-induced cardiotoxicity, partlyviainhibiting Nrf2-dependent ferroptosis.
Experiment 15 Reporting the Ferroptosis Target of This Regulator				[26]
Responsed Disease	Osteonecrosis		ICD-11: FB81	Disease Info
Responsed Drug	Zoledronic acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
Response regulation	FBXO9 was downregulated in Zoledronic acid-treated osteoclast and promoted osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation. The study provided a possible theoretical target for the clinical treatment of Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ).
Experiment 16 Reporting the Ferroptosis Target of This Regulator				[27]
Responsed Disease	Lung injury		ICD-11: NB32	Disease Info
Responsed Drug	Lipopolysaccharide		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
Response regulation	Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury.
Experiment 17 Reporting the Ferroptosis Target of This Regulator				[35]
Responsed Disease	Acute myeloid leukaemia		ICD-11: 2A60	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	hBMSCs (Bone marrow stromal cells)
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	MOLM-13 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
In Vivo Model	All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 10⁶, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured. Click to Show/Hide
Response regulation	The overexpression of circKDM4C in acute myeloid leukemia (AML) cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53.
Experiment 18 Reporting the Ferroptosis Target of This Regulator				[36]
Responsed Disease	Osteosarcoma		ICD-11: 2B51	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	IMR-90 cells	Normal	Homo sapiens	CVCL_0347
Response regulation	SOCS1 impacts the pattern of secreted products in cells with active p53 and is required for the expression of a selective set of p53 target genes including those involved in ferroptosis. SOCS1 can use several mechanisms to activate p53, including promotion of serine-15 phosphorylation by ATM/ATR kinases and inhibition of the p53 repressor KAP1 in osteosarcoma cell lines.
Experiment 19 Reporting the Ferroptosis Target of This Regulator				[37]
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
	4T1 cells	Mammary carcinoma	Mus musculus	CVCL_0125
In Vivo Model	BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 10⁵ cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 10⁵ cells/mouse) and mammary carcinoma 4T1 (2 x 10⁴ cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection. Click to Show/Hide
Response regulation	ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment.
Experiment 20 Reporting the Ferroptosis Target of This Regulator				[38]
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Hippo signaling pathway			hsa04390
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
Response regulation	CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Collectively, a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer.
Experiment 21 Reporting the Ferroptosis Target of This Regulator				[39]
Responsed Disease	Hepatocellular carcinoma		ICD-11: 2C12	Disease Info
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 regulation	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.
Experiment 22 Reporting the Ferroptosis Target of This Regulator				[40]
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Pathway Response	Cell adhesion molecules			hsa04514
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H358 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	The 4-wk-old female nude mice used in this study were purchased from Hunan SJA Laboratory Animal Co., Ltd (Changsha). Then, 2 x 10⁶ GINS4 WT or KO A549 cells were injected s.c. into nude mice without matrigel. Tumor size was measured every 2 d with a caliper, and volume of tumor was calculated with the formula: L x W2 x 0.5, for L represents the longest diameter and W means the shortest diameter. Then, 2 x 10⁶ p53 WT and KO A549 cells with shCon or shGINS4 overexpressing were injected s.c. into nude mice without matrigel. When tumors reached 60 to 100 mm³, p53 WT with shGINS4 mice were treated with ferrostatin-1 (S7243, Selleckchem) (20 mg/kg) in 2% DMSO, 50% PEG300, 5% Tween80, and 43% water by daily intraperitoneal injection. Tumors were measured three times a week. Mice were sacrificed and tumors were collected finally. Tumor tissue was made into a single-cell suspension for lipid ROS assay using Tumor Dissociation Kit (Miltenyi Biotec). Click to Show/Hide
Response regulation	GINS4 is a potential oncogene in lung adenocarcinoma (LUAD) that functions to destabilize p53 and then inhibits ferroptosis, providing a potential therapeutic target for LUAD.
Experiment 23 Reporting the Ferroptosis Target of This Regulator				[41]
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	SPC-A1 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	NCI-H522 cells	Non-small cell lung carcinoma	Homo sapiens	CVCL_1567
	HBE1 cells	Normal	Homo sapiens	CVCL_0287
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	MRC-5 cells	Normal	Homo sapiens	CVCL_0440
	NCI-H358 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	95C cells	Lung giant cell carcinoma	Homo sapiens	CVCL_7109
	95D cells	Lung giant cell carcinoma	Homo sapiens	CVCL_7110
In Vivo Model	SCID mice (Hunan SJA Laboratory Animal Co. Ltd.) were injected with the indicated cells in the mammary fat pad (10 mice/group). Injected mice were imaged from both the dorsal and ventral sides every three days. Click to Show/Hide
Response regulation	P53RRA bound Ras GTPase-activating protein-binding protein 1 (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of G3BP1 (aa 177-466). The cytosolic P53RRA-G3BP1 interaction displaced p53 from a G3BP1 complex, resulting in greater p53 retention in the nucleus, which led to cell-cycle arrest, apoptosis, and ferroptosis in lung cancer cell lines.
Experiment 24 Reporting the Ferroptosis Target of This Regulator				[42]
Responsed Disease	Cerebral ischemia		ICD-11: 8B10	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Wild-type SD rats were kept in the Animal Experiment Center of Southeast University. Experimental rats were divided into 4 groups (n = 6 per group). The method of establishing the I/R model was provided in supplementary material. Then, we covered the ligation with gel. In order to fully cover the infarcted area of the heart, we chose to inject about 300 uL of mimics + Gel at 23 mm below the left atrial appendage (about the ligation). In order to prevent excessive irradiation of tissue burns, we selected each irradiation for 2 min to control the body surface temperature for a total of 10 min of irradiation. Click to Show/Hide
Response regulation	The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in ischemia-reperfusion (I/R) model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.
Experiment 25 Reporting the Ferroptosis Target of This Regulator				[43]
Responsed Disease	Cerebral ischaemic stroke		ICD-11: 8B11	Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	rRBMECs (Rat brain microvascular endothelial cells)
In Vivo Model	Sprague Dawley (SD) rats (n = 60) aged three weeks were purchased from the Experimental Animal Center of Xiangya Hospital of Central South University. All rats were bred in a specific pathogen-free environment in 12-h lightdark cycle and fed with rodent diet and water. All rats were anaesthetized with inhaling isoflurane (2%, CAS NO. 64181101, Lunan Pharmaceutical Co., LTD. Shandong, China) and sacrificed by cervical dislocation. The whole brain was removed after opening the cranial cavity. Click to Show/Hide
Response regulation	OGD combined with hyperglycemic reperfusion promoted Meg3 expression and there was positive correlation between Meg3 and p53 expression in RBMVECs. Subsequently, p53 inhibited the activity of GPX4 by binding with its promoter. The Meg3- p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion and Meg3 has been considered as an important mediator in regulating diabetic brain ischemic injury.
Experiment 26 Reporting the Ferroptosis Target of This Regulator				[44]
Responsed Disease	Cerebral ischaemic stroke		ICD-11: 8B11	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 regulation	PVT1 regulates ferroptosis through miR-214-mediated p53 and TFR1. The discovery of PVT1 and miR-214 as potential targets for I/R also implies that PVT1 and miR-214 play critical roles in ferroptosis, shedding new light on the mechanism of ferroptosis in acute ischemic stroke.
Experiment 27 Reporting the Ferroptosis Target of This Regulator				[45]
Responsed Disease	Chronic heart failure		ICD-11: BD1Z	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Necroptosis			hsa04217
	NF-kappa B signaling pathway			hsa04064
Cell Process	Cell ferroptosis
	Cell pyroptosis
In Vitro Model	rHTs (Rat hippocampal tissues)
In Vivo Model	Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively. Click to Show/Hide
Response regulation	MLK3 (MAP3K11) mainly regulates the JNK/ p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC.
Experiment 28 Reporting the Ferroptosis Target of This Regulator				[46]
Responsed Disease	Health		ICD-11: N.A.	Disease Info
Responsed Drug	Alumina		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hHCs (Hippocampal cells)
In Vivo Model	Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. Click to Show/Hide
Response regulation	Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis.
Experiment 29 Reporting the Ferroptosis Target of This Regulator				[46]
Responsed Disease	Health		ICD-11: N.A.	Disease Info
Responsed Drug	R46A2		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hHCs (Hippocampal cells)
In Vivo Model	Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. Click to Show/Hide
Response regulation	Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis.
Experiment 30 Reporting the Ferroptosis Target of This Regulator				[47]
Responsed Disease	Traumatic brain injury		ICD-11: NA07	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	The Experimental Animal Center at Southern Medical University provided the wild-type (WT) adult male and female C57BL/6 mice (body weight, 22-25 g). Briefly, mice were anesthetized with an intraperitoneal injection of sodium pentobarbital (30 mg/kg), and mounted on a stereotaxic frame. A midsagittal incision was made in the scalp and a circular craniotomy (4.5 mm diameter) was made over the left parietotemporal cortex. Click to Show/Hide
Response regulation	P53-mediated ferroptosis contributes to the pathogenesis of traumatic brain injury (TBI). Furthermore, SIRT2 exerts a neuroprotective effect against TBI by suppressing p53-mediated ferroptosis.

Transferrin receptor protein 1 (TFRC) [Driver; Suppressor; Marker]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[28]
Target for Ferroptosis	Marker/Suppressor/Driver
Responsed Disease	Ischemia/reperfusion injury		ICD-11: DB98	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Male Sprague-Dawley (SD) rats (250-300 g) were purchased from the Laboratory Animal Center, Xiangya School of Medicine, Central South University, China. Briefly, a left thoracotomy was carried out in the fourth intercostal space and the heart was exposed via opening the pericardium. The left coronary artery was around via 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. Click to Show/Hide
Response regulation	A novel pathway of USP7/ p53/TfR1 has been identified in the ischemia/reperfusion (I/R)-treated rat hearts, where up-regulation of USP7 promotes ferrptosis via activation of the p53/TfR1 pathway.

Polyunsaturated fatty acid lipoxygenase ALOX15 (ALOX15) [Driver]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[29]
Target for Ferroptosis	Driver
Responsed Disease	Spinal cord injury		ICD-11: ND51	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	Forty female Sprague-Dawley rats (200-300 g, 8 weeks old) were purchased from the Animal Experiment Center of Fudan University. Forty rats were randomly divided into four groups: sham operation group (n = 10), SCI group (n = 10), SCI + ferroptosis inhibitor group (SCI + ferrostatin1) (n = 10), and SCI + DHODH Inhibitor group (SCI + teriflunomide) (n = 10). Ten rats in the sham group only received laminectomy without SCI. To induce spinal cord injury, spinal cord injury surgery was performed in the middle thoracic region of rats (T8-T9). Click to Show/Hide
Response regulation	The application of DHODH is a potential treatment for spinal cord injury (SCI). DHODH can reduce the ferroptosis of neurons after spinal cord injury by regulating the P53/ALOX15 signaling pathway, thereby alleviating spinal cord injury.

Mitoferrin-2 (SLC25A28) [Driver]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[33]
Target for Ferroptosis	Driver
Responsed Disease	Liver fibrosis		ICD-11: DB93	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	hHSCs (Human hepatic stellate cells)
	HSC-T6 cells	Normal	Rattus norvegicus	CVCL_0315
In Vivo Model	Eight-week-old male C57BL/6 mice were purchased from Nanjing Medical University (Nanjing, China). Sixty mice were randomly divided into six groups of ten animals each with comparable mean body weight. Mice of six groups were treated with Sham, BDL + VA-Lip-Control-shRNA, BDL + VA-Lip-Control-shRNA + erastin, BDL + VA-Lip-BRD7-shRNA + erastin, BDL + VA-Lip-P53-shRNA + erastin or BDL + VA-Lip-SLC25A28-shRNA + erastin, respectively. Mice were anesthetized with isoflurane. A midline laparotomy was performed, and the common bile duct was ligated close to the liver hilus immediately below the bifurcation with 3-0 surgical silk and cut between the ligatures as described previously. Click to Show/Hide
Response regulation	BRD7- P53-SLC25A28 axis involves in mediating ferroptosis via mitochondrial iron metabolism pathway. These findings reveal novel signal transduction and regulatory mechanism of ferroptosis, and also suggest BRD7- P53-SLC25A28 axis as potential targets for liver fibrosis.

Glioblastoma [ICD-11: 2A00]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[4]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[5]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[6]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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
	HOS cells	Osteosarcoma	Homo sapiens	CVCL_0312
Response regulation	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.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[36]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	IMR-90 cells	Normal	Homo sapiens	CVCL_0347
Response regulation	SOCS1 impacts the pattern of secreted products in cells with active p53 and is required for the expression of a selective set of p53 target genes including those involved in ferroptosis. SOCS1 can use several mechanisms to activate p53, including promotion of serine-15 phosphorylation by ATM/ATR kinases and inhibition of the p53 repressor KAP1 in osteosarcoma cell lines.

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

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[1]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Quisinostat		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Necroptosis			hsa04217
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
	Cell pyroptosis
In Vitro Model	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
	Tca8113 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
In Vivo Model	Adult male athymic BALB/c nude mice (20-22 g of 5-week-old mice) were housed in a controlled environment at 23 ± 2 and 40%-70% humidity under a 12 h dark/light cycle with free access to irradiated food and sterile water. A suspension of 6 x 10⁶/100 uL TCA-8113 cells was inoculated subcutaneously into the hind flank region of each nude mouse. The average tumor volume in nude mice reached 100 mm³, and mice were randomly divided into three groups. Quisinostat was formulated in normal saline and administered at 3 and 10 mg/kg/day byintraperitoneal injection. Control mice were given equal volume saline intraperitoneally. The tumor volume and the bodyweight of mice were monitored every three days. Click to Show/Hide
Response regulation	Quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.

Gastric cancer [ICD-11: 2B72]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[7]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[8]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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]

Disease Info

In total 3 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[9]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[23]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Clioquinol		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	PI3K-Akt signaling pathway			hsa04151
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	SK-N-SH cells	Neuroblastoma	Homo sapiens	CVCL_0531
In Vivo Model	In total, twelve healthy adult rhesus monkeys (Macaca mulatta lasiotis, aged 4-5 years, and weighed 3.5-5 kg at the start of the study) were obtained from Sichuan Primed Biological Technology Co., Ltd. Monkeys were randomly divided into two groups: normal (control) group (n = 3) and MPTP group (n = 9). Monkeys from MPTP group were administered with MPTP by intramuscular injection daily at the beginning of the study, and then the MPTP dose was gradually added to 0.5 mg/kg at the end of the experiment. Monkeys from control group were injected with saline instead, and the other conditions were the same with MPTP group. Click to Show/Hide
Response regulation	Ferroptosis was probably involved in the pathogenesis of parkinson's disease (PD). Clioquinol (CQ) can decrease the excessive iron in the SN to normal level and directly protect DA neurons against oxidative stress probably by activating the AKT/mTOR survival pathway and blocking p53-medicated cell death.
Experiment 3 Reporting the Ferroptosis-centered Disease Response				[24]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Ferric ammonium citrate		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	MES23.5 cells	Normal	Mus musculus	CVCL_J351
In Vivo Model	Human a-synuclein (a-Syn) A53T overexpressiontransgenic mice(B6; C3-Tg (Prnp-SNCA*A53T) 83Vle/J) were originally obtained in breeding pairs from the Jackson Laboratory (004479) to generate a stable breeding colony. Animals were raised according to SPF level, kept at constant temperature (20 ± 2) , constant humidity (50 ± 10%), day and night cycle light (12-12 h), with free access to food and water. Click to Show/Hide
Response regulation	Ferroptosis firstly occurred in a relatively low concentration of ferric ammonium citrate (FAC)-treated group, and then apoptosis appeared in response to the increased iron doses. This was also confirmed in vivo in parkinson's disease transgenic mice and the underlying mechanism might be associated with the p53 signaling pathway, but not MAPK signaling pathway.

Status epilepticus [ICD-11: 8A66]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[2]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Apigenin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	SH-SY5Y cells	Neuroblastoma	Homo sapiens	CVCL_0019
In Vivo Model	5-weeks-old kainate (KA)-induced BALB/c nude mice, a widely used epilepsy mouse model, were performed with intraperitoneal (i.p.) injection of KA (6 mg/kg). Pre-treatment 21 with antioxidant apigenin (60 mg/Kg, 2 days) or post-treatment with apigenin (60 mg/Kg, 1 day), mice were injected with KA (6 mg/kg) via intraperitoneal (i.p.) injection, and then HCP (0.5 mg/Kg) were injected by intravenous (i.v.) injection. In vivo and Ex vivo fluorescence images of relative ClO levels in mice brains 5, 15, 30, 45, and 60 min post injection of HCP were further performed by using the IVIS Spectrum imaging system (Nanjing University) with an excitation filter of 430 nm and the collection wavelength range is from 500-600 nm. Click to Show/Hide
Response regulation	Apigenin can efficiently reduce the expression of intracellular MPO and increase the levels of GPX4 and SIRT1, thereby conferring neuroprotection through regulation of kainic acid (KA)-induced ferroptosis. And the level of Ac-p53 inside the brains treated with apigenin was down-regulated, suggesting that the p53-mediated ferroptosis pathway might be blocked. Overall, apigenin was screened and confirmed as an efficient lead compound for epilepsy prevention and treatment.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[10]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[11]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[12]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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.

Neurotoxicity [ICD-11: NE61]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response			[3]
Target Regulator	Cellular tumor antigen p53 (TP53)	Protein coding	Regulator Info
Responsed Drug	Sevoflurane	Approved	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	Pregnant rats were placed in a dedicated plastic chamber with ambient gas at a flow rate of 2L/min. Fer-1 solubilized in saline and 1% dimethyl sulfoxide (DMSO) and PD146176 (a specific 15LOX inhibitor) dissolved in corn oil containing 1% DMSO were administered intraperitoneally to rats at a dose of 5 mg/kg 1 h before each exposure, respectively. Similarly, 0.5 mg/kg Ku55933 (an ATM inhibitor), which is diluted in saline containing 1% DMSO, was intraperitoneally administered 2 h previously. Click to Show/Hide
Response regulation	Sevoflurane could enhance 15LO2-PEBP1 interaction and activate ATM and its downstream P53/SAT1 pathway, which might be attributed to excessive p-ATM nuclear translocation, indicating a potential therapeutic target for ameliorating sevoflurane-induced neurotoxicity.

HIV Infection [ICD-11: 1C60]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[13]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Methamphetamine		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
Response regulation	Methamphetamine (METH) and HIV-1 lead to oxidative stress and their combined effect increases the risk of HIV-associated neurocognitive disorder (HAND), which may be related to the synergistic ferroptotic impairment in microglia. We found that METH and HIV-1 Tat reduced the expression of ferroptotic protein GPX4 and the cell viability and enhanced the expression of P53 and the level of ferrous iron, while the above indices were significantly improved with pretreatment of ferrostatin-1.

Colon cancer [ICD-11: 2B90]

Disease Info

In total 5 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[14]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Albiziabioside A		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	hBMECs (Human brain microvascular endothelial cells)
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	HaCaT cells	Normal	Homo sapiens	CVCL_0038
	HCT-8 cells	Ileocecal adenocarcinoma	Homo sapiens	CVCL_2478
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	CCD-841CoN cells	Normal	Homo sapiens	CVCL_2871
	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
	BEL-7402 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
In Vivo Model	A total of 1 x 10⁷ HCT116 cells were subcutaneously inoculated into the right flank of BALB/c mice. When tumor reached 70-100 mm³ (10 days after implant), mice were divided into five groups of eight animals at random. The groups with D13 were administered intravenously 20 mg/kg and 10 mg/kg. The positive control group was treated with AlbA(20 mg/kg and 10 mg/kg) through intravenous injection. The negative control group received 0.9% normal saline through intravenous injection. Click to Show/Hide
Response regulation	The study synthesized a series of Albiziabioside A derivatives and evaluated the antitumor activity both in vitro and in vivo. Compound D13 could induce apoptosis and ferroptosis through the mitochondrial pathway as a p53 activator. In addition, compound D13 significantly suppressed tumorigenesis without inducing toxicity in normal organs in vivo. The antitumor efficacy of D13 was further verified in colon cancer xenograft mouse models.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[15]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Ginkgo biflavones		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	RKO cells	Colon carcinoma	Homo sapiens	CVCL_0504
	LoVo cells	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	HCT-116 cells (5 x 10⁶) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately). Click to Show/Hide
Response regulation	Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.
Experiment 3 Reporting the Ferroptosis-centered Disease Response				[30]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ubiquitin mediated proteolysis			hsa04120
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	HeLa cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0030
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	HIEC-6 cells	Normal	Homo sapiens	CVCL_6C21
Response regulation	RRM1 increases the instability of p53 by regulating the physical interaction of p53 with the ubiquitinating enzyme MDM2 and the deubiquitinating enzyme USP11, subsequently suppressing p21 (CDKN1A) and GPX4 in colon carcinoma cells, thereby promoting the accumulation of lipid peroxidation and occurrence of radiation-induced ferroptosis.
Experiment 4 Reporting the Ferroptosis-centered Disease Response				[37]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
In Vitro Model	4T1 cells	Mammary carcinoma	Mus musculus	CVCL_0125
In Vivo Model	BALB/c and C57BL/6 mice were obtained from the Jackson Laboratory (Bar Harbor, ME). To establish subcutaneous tumor models, CT26 cells (2 x 10⁵ cells/mouse) were injected into the right flanks of BALB/c mice. For experimental lung metastasis models, colon carcinoma CT26, mesothelioma AB1 (2 x 10⁵ cells/mouse) and mammary carcinoma 4T1 (2 x 10⁴ cells/mouse) were injected into BALB/c mice. Tumor-bearing mice were treated with vehicle PEG300 (Sigma-Aldrich) and NC06 (dissolved in PEG300), respectively, every two days for 3-5 times by Intraperitoneal injection. Click to Show/Hide
Response regulation	ASAH2 is overexpressed in MDSCs in human colon cancer patients. ASAH2 protects MDSCs from ferroptosis through destabilizing p53 protein to suppress the p53 pathway in MDSCs in the tumor microenvironment.
Experiment 5 Reporting the Ferroptosis-centered Disease Response				[38]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Hippo signaling pathway			hsa04390
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
In Vitro Model	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
Response regulation	CYGB significantly increased the sensitivity of cancer cells to RSL3- and erastin-induced ferroptotic cell death. Collectively, a novel tumour suppressor role of CYGB through p53-YAP1 axis in regulating ferroptosis and suggested a potential therapeutic approach for colon cancer.

Colorectal cancer [ICD-11: 2B91]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[16]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	BEBT-908		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	MC-38 cells	Colon adenocarcinoma	Homo sapiens	CVCL_B288
In Vivo Model	About 2 x 10⁵ MC38 tumor cells were inoculated subcutaneously into C57BL/6 mice. A total of 100 mg/kg BEBT-908 was intravenously injected every other day for four times initiating from day 4 after tumor cell inoculation. Tumors were harvested on day 12 after inoculation, weighted, mechanically minced and incubated with 50 ug/mL DNase I (Sigma) and 2 mg/mL collagenase P (Sigma) for 20 minutes at 37. Click to Show/Hide
Response regulation	Treatment with BEBT-908 promoted ferroptotic cell death of cancer cells by hyperacetylating p53 and facilitating the expression of ferroptotic signaling. The dual PI3K/HDAC inhibitor BEBT-908 elicits potent antitumor responses, effectively inducing immunogenic ferroptosis of colorectal cancer cells and potentiating cancer immunotherapy.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[31]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Ferroptosis			hsa04216
	MAPK signaling pathway			hsa04010
	Fatty acid metabolism			hsa01212
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
	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
In Vivo Model	Six 4-week-old male BALB/c nude mice were ordered from the Shanghai Laboratory Animal Center (Shanghai SLAC Laboratory Animal Co., Ltd., China). A total of 5 x 10⁶ TIPE+/+ SW480 cells were suspended in 100 uL of PBS and subcutaneously injected into the right axilla flank of each nude mouse, and the same amount of vector SW480 cells was into the left. At 2 weeks after inoculation, the xenograft tumor size was measured using Vernier calipers every 2 days. Click to Show/Hide
Response regulation	MiR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. In addition, SAPK/JNK is the upstream molecule of p53. MiR-539 is a new therapeutic target for colorectal cancer (CRC) patients.

Pancreatic cancer [ICD-11: 2C10]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[17]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Dihydroartemisinin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
In Vivo Model	Six to eight-week-old female C57BL/6 mice were purchased from the Experimental Animal Center of Military Medical Sciences (Beijing, China). C57BL/6 mice were anesthetized and the tail of the pancreas was exposed. Panc 02 cells were resuspended in PBS at a concentration of 1 x 10⁶ cells/0.1 ml and 50 ul cells were injected into the tail of the pancreas. Tumor-bearing mice were randomly divided into two groups (3 days after implantation). The control group was intraperitoneally injected 200 ul PBS daily for 10 days, and the DHA group was intraperitoneally injected with 100 mg/kg DHA daily for 10 days. The pancreatic tumors and spleens of the mice were collected for subsequent analysis. Click to Show/Hide
Response regulation	Dihydroartemisinin has anti-tumor effect in pancreatic cancer cells in vitro and in vivo. DHA treatment induced ferroptosis by increasing P53 and AOLX12 expression.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[32]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
Response regulation	Cold induction promotes the process of ferroptosis by inducing the expression of CIRBP and then regulating key factors such as p53 and GPX4[. In addition, cold induction significantly inhibited the proliferation of pancreatic cancer cells and induced cell apoptosis, but after the addition of ferroptosis inhibitor, cell proliferation and apoptosis did not change significantly.

Lung cancer [ICD-11: 2C25]

Disease Info

In total 3 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[18]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Levobupivacaine		Approved	Drug Info
Pathway Response	Ferroptosis			hsa04216
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vitro Model	A427 cells	Lung carcinoma	Homo sapiens	CVCL_1055
In Vivo Model	Balb/c nude mice (n= 5, 4-week-old, male) were applied to detect the impact of levobupivacaine on tumor growth. Mice subcutaneously injected with 1 x 10⁷ A549 cells were treated with levobupivacaine (40 umol/Kg) or equal volume saline. The tumor volume was remarked every 5 days and finished at 30 days after injection, followed by the analysis of volume (length (width/2)2) and weight. Click to Show/Hide
Response regulation	Levobupivacaine could inhibit the proliferation and induce the apoptosis of non-small cell lung cancer (NSCLC) cells. Levobupivacaine was able to attenuate the invasion and migration in the cells. The treatment of levobupivacaine remarkably increased the levels of ROS, iron, and Fe2+ in NSCLC cells. Mechanically, levobupivacaine up-regulated the expression of p53 and induced ferroptosis by regulating p53 in NSCLC cells.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[40]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Cell adhesion molecules			hsa04514
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	NCI-H358 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
In Vivo Model	The 4-wk-old female nude mice used in this study were purchased from Hunan SJA Laboratory Animal Co., Ltd (Changsha). Then, 2 x 10⁶ GINS4 WT or KO A549 cells were injected s.c. into nude mice without matrigel. Tumor size was measured every 2 d with a caliper, and volume of tumor was calculated with the formula: L x W2 x 0.5, for L represents the longest diameter and W means the shortest diameter. Then, 2 x 10⁶ p53 WT and KO A549 cells with shCon or shGINS4 overexpressing were injected s.c. into nude mice without matrigel. When tumors reached 60 to 100 mm³, p53 WT with shGINS4 mice were treated with ferrostatin-1 (S7243, Selleckchem) (20 mg/kg) in 2% DMSO, 50% PEG300, 5% Tween80, and 43% water by daily intraperitoneal injection. Tumors were measured three times a week. Mice were sacrificed and tumors were collected finally. Tumor tissue was made into a single-cell suspension for lipid ROS assay using Tumor Dissociation Kit (Miltenyi Biotec). Click to Show/Hide
Response regulation	GINS4 is a potential oncogene in lung adenocarcinoma (LUAD) that functions to destabilize p53 and then inhibits ferroptosis, providing a potential therapeutic target for LUAD.
Experiment 3 Reporting the Ferroptosis-centered Disease Response				[41]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	SPC-A1 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
	NCI-H522 cells	Non-small cell lung carcinoma	Homo sapiens	CVCL_1567
	HBE1 cells	Normal	Homo sapiens	CVCL_0287
	NCI-H1299 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0060
	MRC-5 cells	Normal	Homo sapiens	CVCL_0440
	NCI-H358 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	95C cells	Lung giant cell carcinoma	Homo sapiens	CVCL_7109
	95D cells	Lung giant cell carcinoma	Homo sapiens	CVCL_7110
In Vivo Model	SCID mice (Hunan SJA Laboratory Animal Co. Ltd.) were injected with the indicated cells in the mammary fat pad (10 mice/group). Injected mice were imaged from both the dorsal and ventral sides every three days. Click to Show/Hide
Response regulation	P53RRA bound Ras GTPase-activating protein-binding protein 1 (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of G3BP1 (aa 177-466). The cytosolic P53RRA-G3BP1 interaction displaced p53 from a G3BP1 complex, resulting in greater p53 retention in the nucleus, which led to cell-cycle arrest, apoptosis, and ferroptosis in lung cancer cell lines.

Ovarian cancer [ICD-11: 2C73]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[19]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Apatinib		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
Response regulation	Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[19]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Olaparib		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
Response regulation	Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis.

Prostate cancer [ICD-11: 2C82]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[20]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Flubendazole		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145 cells	Prostate carcinoma	Homo sapiens	CVCL_0105
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	RWPE-1 cells	Normal	Homo sapiens	CVCL_3791
In Vivo Model	24 nude mice (3-4 weeks) were acquired from the experimental animal center of southern medical university (GuangZhou, China) and kept under specific pathogen-free conditions. 4 x 10⁶ PC3 cells were implanted subcutaneously into the right armpit regions of each nude mouse. When the tumors volume reached approximately 40 mm³, mice were randomly divided into two groups to receive flubendazole (10 mg/kg, once daily), 5-fluorouracil (30 mg/kg, once daily), their combination, and vehicle control by intraperitoneal injection. After 20 days of treatment, all mice were sacrificed and tumor weight and tumor volume were immediately measured, respectively. Click to Show/Hide
Response regulation	Flubendazole is a novel P53 inducer which exerts anti-proliferation and pro-apoptosis effects in castration-resistant prostate cancer (CRPC) through hindering the cell cycle and activating the ferroptosis, and indicates that a novel utilization of flubendazole in neoadjuvant chemotherapy of CRPC.

Hereditary Leiomyomatosis [ICD-11: 2C90]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[21]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Artesunate		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	Caki-1 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	786-O cells	Renal cell carcinoma	Homo sapiens	CVCL_1051
	KTCTL-26 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_5872
	A-498 cells	Renal cell carcinoma	Homo sapiens	CVCL_1056
Response regulation	Artesunate (ART) significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant renal cell carcinoma (RCC) cells. P53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.

Adrenocortical carcinoma [ICD-11: 2D11]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[22]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Romidepsin		Investigative	Drug Info
Pathway Response	Cell adhesion molecules			hsa04514
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	SW13 cells	Adrenal cortex carcinoma	Homo sapiens	CVCL_0542
Response regulation	HDAC inhibitor Romidepsin converted SW13+ cells also had reduced mRNA expression of the mitochondrial ROS detoxifier superoxide dismutase 2 (SOD2), and the tumor suppressor p53. HDAC inhibitor treatment synergistically increased adrenocortical carcinoma cell death following induction of ferroptosis.

Cardiomyopathy [ICD-11: BC43]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[25]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Berberine		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	All animal experiment protocols were implemented in accordance with the National Institutes of Health (NIH) guidelines, and the procedures were approved by the Animal Ethics Committee of Southwest University. C57BL/6J male mice, 8-10 weeks old, weighing 20 ± 2 g, were used in this study. Mice were housed under standard conditions at 22-24 with a 12 h light/12 h darkness cycle and free access to food and tap water. Thirty-six mice were randomly divided into six groups: control (N = 8), IMA group (50 mg/kg) (N = 8), Low-Ber (20 mg/kg) + IMA group (N = 8), Medium-Ber (40 mg kg1) + IMA group (N = 8), High-Ber (80 mg/kg) + IMA group (N = 8), and Fer-1 (1 mg/kg) + IMA group (N = 8). IMA was given intraperitoneally for 14 days. Ber was given orally 2 h before IMA treatment and Fer-1 was given intraperitoneally 2 h before IMA treatment. Click to Show/Hide
Response regulation	Berberine downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against IMA-induced cardiotoxicity, partlyviainhibiting Nrf2-dependent ferroptosis.

Liver fibrosis [ICD-11: DB93]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[33]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	hHSCs (Human hepatic stellate cells)
	HSC-T6 cells	Normal	Rattus norvegicus	CVCL_0315
In Vivo Model	Eight-week-old male C57BL/6 mice were purchased from Nanjing Medical University (Nanjing, China). Sixty mice were randomly divided into six groups of ten animals each with comparable mean body weight. Mice of six groups were treated with Sham, BDL + VA-Lip-Control-shRNA, BDL + VA-Lip-Control-shRNA + erastin, BDL + VA-Lip-BRD7-shRNA + erastin, BDL + VA-Lip-P53-shRNA + erastin or BDL + VA-Lip-SLC25A28-shRNA + erastin, respectively. Mice were anesthetized with isoflurane. A midline laparotomy was performed, and the common bile duct was ligated close to the liver hilus immediately below the bifurcation with 3-0 surgical silk and cut between the ligatures as described previously. Click to Show/Hide
Response regulation	BRD7- P53-SLC25A28 axis involves in mediating ferroptosis via mitochondrial iron metabolism pathway. These findings reveal novel signal transduction and regulatory mechanism of ferroptosis, and also suggest BRD7- P53-SLC25A28 axis as potential targets for liver fibrosis.

Ischemia/reperfusion injury [ICD-11: DB98]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[28]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Male Sprague-Dawley (SD) rats (250-300 g) were purchased from the Laboratory Animal Center, Xiangya School of Medicine, Central South University, China. Briefly, a left thoracotomy was carried out in the fourth intercostal space and the heart was exposed via opening the pericardium. The left coronary artery was around via 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. Click to Show/Hide
Response regulation	A novel pathway of USP7/ p53/TfR1 has been identified in the ischemia/reperfusion (I/R)-treated rat hearts, where up-regulation of USP7 promotes ferrptosis via activation of the p53/TfR1 pathway.

Osteonecrosis [ICD-11: FB81]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[26]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Zoledronic acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
Response regulation	FBXO9 was downregulated in Zoledronic acid-treated osteoclast and promoted osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation. The study provided a possible theoretical target for the clinical treatment of Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ).

Lung injury [ICD-11: NB32]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[27]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Responsed Drug	Lipopolysaccharide		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
Response regulation	Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[34]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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.

Spinal cord injury [ICD-11: ND51]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[29]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator 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	Forty female Sprague-Dawley rats (200-300 g, 8 weeks old) were purchased from the Animal Experiment Center of Fudan University. Forty rats were randomly divided into four groups: sham operation group (n = 10), SCI group (n = 10), SCI + ferroptosis inhibitor group (SCI + ferrostatin1) (n = 10), and SCI + DHODH Inhibitor group (SCI + teriflunomide) (n = 10). Ten rats in the sham group only received laminectomy without SCI. To induce spinal cord injury, spinal cord injury surgery was performed in the middle thoracic region of rats (T8-T9). Click to Show/Hide
Response regulation	The application of DHODH is a potential treatment for spinal cord injury (SCI). DHODH can reduce the ferroptosis of neurons after spinal cord injury by regulating the P53/ALOX15 signaling pathway, thereby alleviating spinal cord injury.

Acute myeloid leukaemia [ICD-11: 2A60]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[35]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	hBMSCs (Bone marrow stromal cells)
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	HL-60 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_0002
	MOLM-13 cells	Adult acute myeloid leukemia	Homo sapiens	CVCL_2119
In Vivo Model	All BALB/C male nude mice (6 weeks old), purchased from Beijing Weitong lihua Experimental Animal Technology Co., Ltd, were maintained in pathogen-free facilities. The K562 or HL-60 cells (3 x 10⁶, 200 ul) transfected with circKDM4C, vector, si-NC, or si-circKDM4C were subcutaneously injected into the right flank of nude mice (9 mice each group) for tumorigenesis. The maximum (Length) and minimum (Width) length of the tumors were measured. Click to Show/Hide
Response regulation	The overexpression of circKDM4C in acute myeloid leukemia (AML) cell lines inhibited the cell proliferation, migration, invasion, and promoted ferroptosis. The expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53.

Hepatocellular carcinoma [ICD-11: 2C12]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[39]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
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 regulation	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.

Cerebral ischemia [ICD-11: 8B10]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[42]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	CHO-S/H9C2 cells	Normal	Cricetulus griseus	CVCL_A0TS
In Vivo Model	Wild-type SD rats were kept in the Animal Experiment Center of Southeast University. Experimental rats were divided into 4 groups (n = 6 per group). The method of establishing the I/R model was provided in supplementary material. Then, we covered the ligation with gel. In order to fully cover the infarcted area of the heart, we chose to inject about 300 uL of mimics + Gel at 23 mm below the left atrial appendage (about the ligation). In order to prevent excessive irradiation of tissue burns, we selected each irradiation for 2 min to control the body surface temperature for a total of 10 min of irradiation. Click to Show/Hide
Response regulation	The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in ischemia-reperfusion (I/R) model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.

Cerebral ischaemic stroke [ICD-11: 8B11]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[43]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	rRBMECs (Rat brain microvascular endothelial cells)
In Vivo Model	Sprague Dawley (SD) rats (n = 60) aged three weeks were purchased from the Experimental Animal Center of Xiangya Hospital of Central South University. All rats were bred in a specific pathogen-free environment in 12-h lightdark cycle and fed with rodent diet and water. All rats were anaesthetized with inhaling isoflurane (2%, CAS NO. 64181101, Lunan Pharmaceutical Co., LTD. Shandong, China) and sacrificed by cervical dislocation. The whole brain was removed after opening the cranial cavity. Click to Show/Hide
Response regulation	OGD combined with hyperglycemic reperfusion promoted Meg3 expression and there was positive correlation between Meg3 and p53 expression in RBMVECs. Subsequently, p53 inhibited the activity of GPX4 by binding with its promoter. The Meg3- p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion and Meg3 has been considered as an important mediator in regulating diabetic brain ischemic injury.
Experiment 2 Reporting the Ferroptosis-centered Disease Response				[44]
Target Regulator	Cellular tumor antigen p53 (TP53)		Protein coding	Regulator 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 regulation	PVT1 regulates ferroptosis through miR-214-mediated p53 and TFR1. The discovery of PVT1 and miR-214 as potential targets for I/R also implies that PVT1 and miR-214 play critical roles in ferroptosis, shedding new light on the mechanism of ferroptosis in acute ischemic stroke.

Chronic heart failure [ICD-11: BD1Z]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response			[45]
Target Regulator	Cellular tumor antigen p53 (TP53)	Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
	Necroptosis		hsa04217
	NF-kappa B signaling pathway		hsa04064
Cell Process	Cell ferroptosis
	Cell pyroptosis
In Vitro Model	rHTs (Rat hippocampal tissues)
In Vivo Model	Male wild-type (WT) C57BL/6J mice aged 8 weeks were obtained from the Experimental Animal Center, Guangzhou University of Chinese Medicine. Sham and TAC mice received corresponding isotype i.p. injections. TAC + AAVMLK3- mice were generated by intravenous (i.v.) injection of adeno-associated viral vector-MLK3 vector (AAVMLK3-) (GenePharma, Shanghai, China) 14 and 21 days before TAC surgery. Sham + AAVNC and TAC + AAVNC mice received AAVNC i.v. injections. TAC + antagomir and TAC + agomir were generated by i.v. injection of antagomir and agomir (30 pmol/g) 14 and 21 days before TAC surgery, respectively. Click to Show/Hide
Response regulation	MLK3 (MAP3K11) mainly regulates the JNK/ p53 signaling pathway-mediated oxidative stress and that ferroptosis causes myocardial fibrosis in the advanced stages of chronic heart failure (CHF). Promoting the expression of miR-351 can inhibit the expression of MLK3, and significantly improve cardiac function in mice subjected to TAC.

Health [ICD-11: N.A.]

Disease Info

In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response			[46]
Target Regulator	Cellular tumor antigen p53 (TP53)	Protein coding	Regulator Info
Responsed Drug	Alumina	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hHCs (Hippocampal cells)
In Vivo Model	Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. Click to Show/Hide
Response regulation	Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response			[46]
Target Regulator	Cellular tumor antigen p53 (TP53)	Protein coding	Regulator Info
Responsed Drug	R46A2	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hHCs (Hippocampal cells)
In Vivo Model	Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. Click to Show/Hide
Response regulation	Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis.

Traumatic brain injury [ICD-11: NA07]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response			[47]
Target Regulator	Cellular tumor antigen p53 (TP53)	Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	The Experimental Animal Center at Southern Medical University provided the wild-type (WT) adult male and female C57BL/6 mice (body weight, 22-25 g). Briefly, mice were anesthetized with an intraperitoneal injection of sodium pentobarbital (30 mg/kg), and mounted on a stereotaxic frame. A midsagittal incision was made in the scalp and a circular craniotomy (4.5 mm diameter) was made over the left parietotemporal cortex. Click to Show/Hide
Response regulation	P53-mediated ferroptosis contributes to the pathogenesis of traumatic brain injury (TBI). Furthermore, SIRT2 exerts a neuroprotective effect against TBI by suppressing p53-mediated ferroptosis.

Sevoflurane [Approved]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response			[3]
Drug for Ferroptosis	Inducer
Response Target	Diamine acetyltransferase 1 (SAT1)	Driver	Target Info
Responsed Disease	Neurotoxicity	ICD-11: NE61	Disease Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	Pregnant rats were placed in a dedicated plastic chamber with ambient gas at a flow rate of 2L/min. Fer-1 solubilized in saline and 1% dimethyl sulfoxide (DMSO) and PD146176 (a specific 15LOX inhibitor) dissolved in corn oil containing 1% DMSO were administered intraperitoneally to rats at a dose of 5 mg/kg 1 h before each exposure, respectively. Similarly, 0.5 mg/kg Ku55933 (an ATM inhibitor), which is diluted in saline containing 1% DMSO, was intraperitoneally administered 2 h previously. Click to Show/Hide
Response regulation	Sevoflurane could enhance 15LO2-PEBP1 interaction and activate ATM and its downstream P53/SAT1 pathway, which might be attributed to excessive p-ATM nuclear translocation, indicating a potential therapeutic target for ameliorating sevoflurane-induced neurotoxicity.

Cyperquat [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[9]
Drug for Ferroptosis	Inducer
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Tanshinone IIA [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[7]
Drug for Ferroptosis	Inducer
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Seratrodast [Discontinued in Phase 3]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[10]
Drug for Ferroptosis	Suppressor
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Apigenin [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[2]
Drug for Ferroptosis	Suppressor
Response Target	Phospholipid hydroperoxide glutathione peroxidase (GPX4)		Suppressor	Target Info
Responsed Disease	Status epilepticus		ICD-11: 8A66	Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	SH-SY5Y cells	Neuroblastoma	Homo sapiens	CVCL_0019
In Vivo Model	5-weeks-old kainate (KA)-induced BALB/c nude mice, a widely used epilepsy mouse model, were performed with intraperitoneal (i.p.) injection of KA (6 mg/kg). Pre-treatment 21 with antioxidant apigenin (60 mg/Kg, 2 days) or post-treatment with apigenin (60 mg/Kg, 1 day), mice were injected with KA (6 mg/kg) via intraperitoneal (i.p.) injection, and then HCP (0.5 mg/Kg) were injected by intravenous (i.v.) injection. In vivo and Ex vivo fluorescence images of relative ClO levels in mice brains 5, 15, 30, 45, and 60 min post injection of HCP were further performed by using the IVIS Spectrum imaging system (Nanjing University) with an excitation filter of 430 nm and the collection wavelength range is from 500-600 nm. Click to Show/Hide
Response regulation	Apigenin can efficiently reduce the expression of intracellular MPO and increase the levels of GPX4 and SIRT1, thereby conferring neuroprotection through regulation of kainic acid (KA)-induced ferroptosis. And the level of Ac-p53 inside the brains treated with apigenin was down-regulated, suggesting that the p53-mediated ferroptosis pathway might be blocked. Overall, apigenin was screened and confirmed as an efficient lead compound for epilepsy prevention and treatment.

Bavachin [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[6]
Drug for Ferroptosis	Inducer
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Ferric citrate [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[12]
Drug for Ferroptosis	Inducer
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Gambogenic Acid [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[8]
Drug for Ferroptosis	Inducer
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Isorhynchophylline [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[11]
Drug for Ferroptosis	Suppressor
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Kayadiol [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[5]
Drug for Ferroptosis	Inducer
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Pseudolaric acid B [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[4]
Drug for Ferroptosis	Inducer
Response Target	Cystine/glutamate transporter (SLC7A11)		Driver; Suppressor	Target Info
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 regulation	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.

Quisinostat [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[1]
Drug for Ferroptosis	Inducer
Response Target	Phospholipid hydroperoxide glutathione peroxidase (GPX4)		Suppressor	Target Info
Responsed Disease	Oral squamous cell carcinoma		ICD-11: 2B6E	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Necroptosis			hsa04217
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
	Cell pyroptosis
In Vitro Model	CAL-27 cells	Tongue adenosquamous carcinom	Homo sapiens	CVCL_1107
	Tca8113 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6851
In Vivo Model	Adult male athymic BALB/c nude mice (20-22 g of 5-week-old mice) were housed in a controlled environment at 23 ± 2 and 40%-70% humidity under a 12 h dark/light cycle with free access to irradiated food and sterile water. A suspension of 6 x 10⁶/100 uL TCA-8113 cells was inoculated subcutaneously into the hind flank region of each nude mouse. The average tumor volume in nude mice reached 100 mm³, and mice were randomly divided into three groups. Quisinostat was formulated in normal saline and administered at 3 and 10 mg/kg/day byintraperitoneal injection. Control mice were given equal volume saline intraperitoneally. The tumor volume and the bodyweight of mice were monitored every three days. Click to Show/Hide
Response regulation	Quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.

Levobupivacaine [Approved]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[18]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Pathway Response	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	A427 cells	Lung carcinoma	Homo sapiens	CVCL_1055
In Vivo Model	Balb/c nude mice (n= 5, 4-week-old, male) were applied to detect the impact of levobupivacaine on tumor growth. Mice subcutaneously injected with 1 x 10⁷ A549 cells were treated with levobupivacaine (40 umol/Kg) or equal volume saline. The tumor volume was remarked every 5 days and finished at 30 days after injection, followed by the analysis of volume (length (width/2)2) and weight. Click to Show/Hide
Response regulation	Levobupivacaine could inhibit the proliferation and induce the apoptosis of non-small cell lung cancer (NSCLC) cells. Levobupivacaine was able to attenuate the invasion and migration in the cells. The treatment of levobupivacaine remarkably increased the levels of ROS, iron, and Fe2+ in NSCLC cells. Mechanically, levobupivacaine up-regulated the expression of p53 and induced ferroptosis by regulating p53 in NSCLC cells.

Flubendazole [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[20]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Prostate cancer		ICD-11: 2C82	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell apoptosis
In Vitro Model	PC-3 cells	Prostate carcinoma	Homo sapiens	CVCL_0035
	DU145 cells	Prostate carcinoma	Homo sapiens	CVCL_0105
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	RWPE-1 cells	Normal	Homo sapiens	CVCL_3791
In Vivo Model	24 nude mice (3-4 weeks) were acquired from the experimental animal center of southern medical university (GuangZhou, China) and kept under specific pathogen-free conditions. 4 x 10⁶ PC3 cells were implanted subcutaneously into the right armpit regions of each nude mouse. When the tumors volume reached approximately 40 mm³, mice were randomly divided into two groups to receive flubendazole (10 mg/kg, once daily), 5-fluorouracil (30 mg/kg, once daily), their combination, and vehicle control by intraperitoneal injection. After 20 days of treatment, all mice were sacrificed and tumor weight and tumor volume were immediately measured, respectively. Click to Show/Hide
Response regulation	Flubendazole is a novel P53 inducer which exerts anti-proliferation and pro-apoptosis effects in castration-resistant prostate cancer (CRPC) through hindering the cell cycle and activating the ferroptosis, and indicates that a novel utilization of flubendazole in neoadjuvant chemotherapy of CRPC.

Albiziabioside A [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[14]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
Cell Process	Cell apoptosis
In Vitro Model	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	hBMECs (Human brain microvascular endothelial cells)
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	HaCaT cells	Normal	Homo sapiens	CVCL_0038
	HCT-8 cells	Ileocecal adenocarcinoma	Homo sapiens	CVCL_2478
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	CCD-841CoN cells	Normal	Homo sapiens	CVCL_2871
	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
	BEL-7402 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_5492
In Vivo Model	A total of 1 x 10⁷ HCT116 cells were subcutaneously inoculated into the right flank of BALB/c mice. When tumor reached 70-100 mm³ (10 days after implant), mice were divided into five groups of eight animals at random. The groups with D13 were administered intravenously 20 mg/kg and 10 mg/kg. The positive control group was treated with AlbA(20 mg/kg and 10 mg/kg) through intravenous injection. The negative control group received 0.9% normal saline through intravenous injection. Click to Show/Hide
Response regulation	The study synthesized a series of Albiziabioside A derivatives and evaluated the antitumor activity both in vitro and in vivo. Compound D13 could induce apoptosis and ferroptosis through the mitochondrial pathway as a p53 activator. In addition, compound D13 significantly suppressed tumorigenesis without inducing toxicity in normal organs in vivo. The antitumor efficacy of D13 was further verified in colon cancer xenograft mouse models.

Apatinib [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[19]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Ovarian cancer		ICD-11: 2C73	Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
Response regulation	Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis.

Artesunate [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[21]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Hereditary Leiomyomatosis		ICD-11: 2C90	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Caki-1 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_0234
	786-O cells	Renal cell carcinoma	Homo sapiens	CVCL_1051
	KTCTL-26 cells	Clear cell renal cell carcinoma	Homo sapiens	CVCL_5872
	A-498 cells	Renal cell carcinoma	Homo sapiens	CVCL_1056
Response regulation	Artesunate (ART) significantly increased cytotoxicity and inhibited proliferation and clonogenic growth in both parental and sunitinib-resistant renal cell carcinoma (RCC) cells. P53 exclusively appeared in the KTCTL-26 cells, indicating that p53 might be predictive for ART-dependent ferroptosis. Thus, ART may hold promise for treating selected patients with advanced and even therapy-resistant RCC.

BEBT-908 [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[16]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Colorectal cancer		ICD-11: 2B91	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	PI3K-Akt signaling pathway			hsa04151
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	MC-38 cells	Colon adenocarcinoma	Homo sapiens	CVCL_B288
In Vivo Model	About 2 x 10⁵ MC38 tumor cells were inoculated subcutaneously into C57BL/6 mice. A total of 100 mg/kg BEBT-908 was intravenously injected every other day for four times initiating from day 4 after tumor cell inoculation. Tumors were harvested on day 12 after inoculation, weighted, mechanically minced and incubated with 50 ug/mL DNase I (Sigma) and 2 mg/mL collagenase P (Sigma) for 20 minutes at 37. Click to Show/Hide
Response regulation	Treatment with BEBT-908 promoted ferroptotic cell death of cancer cells by hyperacetylating p53 and facilitating the expression of ferroptotic signaling. The dual PI3K/HDAC inhibitor BEBT-908 elicits potent antitumor responses, effectively inducing immunogenic ferroptosis of colorectal cancer cells and potentiating cancer immunotherapy.

Berberine [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[25]
Drug for Ferroptosis	Suppressor
Response Target	Unspecific Target
Responsed Disease	Cardiomyopathy		ICD-11: BC43	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	All animal experiment protocols were implemented in accordance with the National Institutes of Health (NIH) guidelines, and the procedures were approved by the Animal Ethics Committee of Southwest University. C57BL/6J male mice, 8-10 weeks old, weighing 20 ± 2 g, were used in this study. Mice were housed under standard conditions at 22-24 with a 12 h light/12 h darkness cycle and free access to food and tap water. Thirty-six mice were randomly divided into six groups: control (N = 8), IMA group (50 mg/kg) (N = 8), Low-Ber (20 mg/kg) + IMA group (N = 8), Medium-Ber (40 mg kg1) + IMA group (N = 8), High-Ber (80 mg/kg) + IMA group (N = 8), and Fer-1 (1 mg/kg) + IMA group (N = 8). IMA was given intraperitoneally for 14 days. Ber was given orally 2 h before IMA treatment and Fer-1 was given intraperitoneally 2 h before IMA treatment. Click to Show/Hide
Response regulation	Berberine downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against IMA-induced cardiotoxicity, partlyviainhibiting Nrf2-dependent ferroptosis.

Clioquinol [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[23]
Drug for Ferroptosis	Suppressor
Response Target	Unspecific Target
Responsed Disease	Parkinson disease		ICD-11: 8A00	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	PI3K-Akt signaling pathway			hsa04151
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	SK-N-SH cells	Neuroblastoma	Homo sapiens	CVCL_0531
In Vivo Model	In total, twelve healthy adult rhesus monkeys (Macaca mulatta lasiotis, aged 4-5 years, and weighed 3.5-5 kg at the start of the study) were obtained from Sichuan Primed Biological Technology Co., Ltd. Monkeys were randomly divided into two groups: normal (control) group (n = 3) and MPTP group (n = 9). Monkeys from MPTP group were administered with MPTP by intramuscular injection daily at the beginning of the study, and then the MPTP dose was gradually added to 0.5 mg/kg at the end of the experiment. Monkeys from control group were injected with saline instead, and the other conditions were the same with MPTP group. Click to Show/Hide
Response regulation	Ferroptosis was probably involved in the pathogenesis of parkinson's disease (PD). Clioquinol (CQ) can decrease the excessive iron in the SN to normal level and directly protect DA neurons against oxidative stress probably by activating the AKT/mTOR survival pathway and blocking p53-medicated cell death.

Dihydroartemisinin [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[17]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Pancreatic cancer		ICD-11: 2C10	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
In Vivo Model	Six to eight-week-old female C57BL/6 mice were purchased from the Experimental Animal Center of Military Medical Sciences (Beijing, China). C57BL/6 mice were anesthetized and the tail of the pancreas was exposed. Panc 02 cells were resuspended in PBS at a concentration of 1 x 10⁶ cells/0.1 ml and 50 ul cells were injected into the tail of the pancreas. Tumor-bearing mice were randomly divided into two groups (3 days after implantation). The control group was intraperitoneally injected 200 ul PBS daily for 10 days, and the DHA group was intraperitoneally injected with 100 mg/kg DHA daily for 10 days. The pancreatic tumors and spleens of the mice were collected for subsequent analysis. Click to Show/Hide
Response regulation	Dihydroartemisinin has anti-tumor effect in pancreatic cancer cells in vitro and in vivo. DHA treatment induced ferroptosis by increasing P53 and AOLX12 expression.

Ferric ammonium citrate [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[24]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Parkinson disease		ICD-11: 8A00	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	MES23.5 cells	Normal	Mus musculus	CVCL_J351
In Vivo Model	Human a-synuclein (a-Syn) A53T overexpressiontransgenic mice(B6; C3-Tg (Prnp-SNCA*A53T) 83Vle/J) were originally obtained in breeding pairs from the Jackson Laboratory (004479) to generate a stable breeding colony. Animals were raised according to SPF level, kept at constant temperature (20 ± 2) , constant humidity (50 ± 10%), day and night cycle light (12-12 h), with free access to food and water. Click to Show/Hide
Response regulation	Ferroptosis firstly occurred in a relatively low concentration of ferric ammonium citrate (FAC)-treated group, and then apoptosis appeared in response to the increased iron doses. This was also confirmed in vivo in parkinson's disease transgenic mice and the underlying mechanism might be associated with the p53 signaling pathway, but not MAPK signaling pathway.

Ginkgo biflavones [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[15]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Colon cancer		ICD-11: 2B90	Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	RKO cells	Colon carcinoma	Homo sapiens	CVCL_0504
	LoVo cells	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	HCT-116 cells (5 x 10⁶) were injected into the flanks of 6-week-old male BALB/c nude mice to generate xenografts. The mice were randomly divided into four groups (n = 7 per group), and treatment was started at 96 h postinjection. The mice received an intraperitoneal injection (i.p.) of 0.9% saline solution containing 5% dimethyl sulfoxide (DMSO) (vehicle for blank control) and ginkgetin (10 mg/kg) once a day, respectively, and 5-FU (30 mg/kg) was used as the positive control (i.p., once every 3 days, alternately). Click to Show/Hide
Response regulation	Ginkgo biflavones can increase the expression level of p53 by inhibiting the expression of MDM2 protein and induce cell death independent of p53 transcriptional activity in vitro. And we provide evidence that ginkgetin strengthened the antitumor effect of fluorouracil (5-FU) in the HCT-116 colon cancer xenograft model.

Lipopolysaccharide [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[27]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Lung injury		ICD-11: NB32	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
Response regulation	Silence of MLK3 (MAP3K11) alleviated Lipopolysaccharide (LPS)-induced lung epithelial cell injury by inhibiting p53-mediated ferroptosis, suggesting that MLK3 may be a potential target to prevent acute lung injury.

Methamphetamine [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[13]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	HIV Infection		ICD-11: 1C60	Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
Response regulation	Methamphetamine (METH) and HIV-1 lead to oxidative stress and their combined effect increases the risk of HIV-associated neurocognitive disorder (HAND), which may be related to the synergistic ferroptotic impairment in microglia. We found that METH and HIV-1 Tat reduced the expression of ferroptotic protein GPX4 and the cell viability and enhanced the expression of P53 and the level of ferrous iron, while the above indices were significantly improved with pretreatment of ferrostatin-1.

Olaparib [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[19]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Ovarian cancer		ICD-11: 2C73	Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
Response regulation	Apatinib combined with olaparib-induced ferroptosis via a p53-dependent manner in ovarian cancer. Further studies showed that apatinib combined with olaparib-induced ferroptosis by inhibiting the expression of Nrf2 and autophagy, thereby inhibiting the expression of GPX4. The Nrf2 activator RTA408 and the autophagy activator rapamycin rescued the combination drug-induced ferroptosis.

Romidepsin [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[22]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Adrenocortical carcinoma		ICD-11: 2D11	Disease Info
Pathway Response	Cell adhesion molecules			hsa04514
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	SW13 cells	Adrenal cortex carcinoma	Homo sapiens	CVCL_0542
Response regulation	HDAC inhibitor Romidepsin converted SW13+ cells also had reduced mRNA expression of the mitochondrial ROS detoxifier superoxide dismutase 2 (SOD2), and the tumor suppressor p53. HDAC inhibitor treatment synergistically increased adrenocortical carcinoma cell death following induction of ferroptosis.

Zoledronic acid [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response				[26]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Osteonecrosis		ICD-11: FB81	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
Response regulation	FBXO9 was downregulated in Zoledronic acid-treated osteoclast and promoted osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation. The study provided a possible theoretical target for the clinical treatment of Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ).

Alumina [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response			[46]
Drug for Ferroptosis	Inducer
Response Target	Unspecific Target
Responsed Disease	Health	ICD-11: N.A.	Disease Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hHCs (Hippocampal cells)
In Vivo Model	Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. Click to Show/Hide
Response regulation	Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis.

R46A2 [Investigative]

Drug Info

In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response			[46]
Drug for Ferroptosis	Suppressor
Response Target	Unspecific Target
Responsed Disease	Health	ICD-11: N.A.	Disease Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	hHCs (Hippocampal cells)
In Vivo Model	Male healthy Wistar rats (six-week-old, provided by Experimental Animal Centre of Harbin Medical University, China) were used in this study. All rats (3-4 rats per cage) access to standard diet anddeionized waterad libitum and were placed in standard laboratory conditions. Seventy-two rats (weighing 200-220 g) were randomly divided into 4 groups (n = 18): AlNPs group was exposed to 50 mg/kg AlNPs (< 50nm, Sigma-Aldrich, USA) by gavage once a day for 90 days. CRS + AlNPs group was received CRS for 21 days and was exposed to 50 mg/kg AlNPs daily by gavage for 90 days. CRS + H2O group was subjected to CRS for 21 days and was given the same volume of deionized water daily by gavage for 90 days. The control (CON) group was given the same volume of deionized water daily and not affected by restraint stress for 90 days. Click to Show/Hide
Response regulation	Alumina nanoparticles (AlNPs) and CRS activated IFN-/ASK1/JNK (MAPK8) signaling pathway. Furthermore, IFN- neutralizing antibody R4-6A2 effectively inhibited the activation of IFN-/ASK1/JNK signaling pathway, alleviated hippocampal neuronal ferroptosis and improved cognition ability. ASK1 inhibitor GS-4997 also improved hippocampal neuronal ferroptosis and cognitive dysfunction by inhibiting ASK1/JNK signaling pathway. JNK inhibits ubiquitin-mediated p53 degradation by increasing phosphorylation of p53 at Ser6, which helps mediate oxidative stress to trigger ferroptosis.

References

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Prof. Shuiping Liu