In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[1]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Icariin		Phase 3	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HL-1 cells	Normal	Mus musculus	CVCL_0303
In Vivo Model	Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group.     Click to Show/Hide
Response Description	Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[2]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Ulinastatin		Phase 3	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In Vivo Model	Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection.     Click to Show/Hide
Response Description	Ulinastatin (UT1) plays a role in mitigation of Acetaminophen (APAP)-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[3]
Regulator for Ferroptosis	Driver
Responsed Drug	Andrographis		Approved	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	RPMI-8226 cells	Plasma cell myeloma	Homo sapiens	CVCL_0014
	U266B1 cells	Plasma cell myeloma	Homo sapiens	CVCL_0566
	AML12 cells	Normal	Mus musculus	CVCL_0140
Response Description	Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 ( MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[4]
Regulator for Ferroptosis	Driver
Responsed Drug	Cetuximab		Approved	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	LoVo cells	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In Vivo Model	The DLD-1 cell suspension (4 x 106 cells/200 ul) was injected subcutaneously into the right dorsal flank of 5-week-old male BALB/c nude mice (Charles River, China). The mice were randomly divided into four groups (5 mice/group): 1) the control group, 2) the RSL3 group, 3) the cetuximab group, and 4) the RSL3 + cetuximab group. Both RSL3 (5 mg/kg) and cetuximab (13 mg/kg) were administered by intraperitoneal injection in a volume of 100 ul once per day. The tumour volume was calculated as 0.5 x length x width2. After 17 days of treatment, the mice were sacrificed, and the tumours were removed. Then, tumour tissue obtained from the different treated groups was subjected to western blotting and immunohistochemical experiments.     Click to Show/Hide
Response Description	Our work reveals that cetuximab enhances the cytotoxic effect of RSL3 on KRAS mutant Colorectal cancer (CRC) cells and that cetuximab enhances RSL3-induced ferroptosis by inhibiting the Nrf2/HO-1 axis through the activation of p38 MAPK.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[5]
Regulator for Ferroptosis	Driver
Responsed Drug	Baicalein		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hCDs (Chondrocytes)
In Vivo Model	C57BL/6J (WT) mice (8 weeks old, male) were purchased from Nanjing Medical university, and AMPK-KO mice were purchased from Shanghai Model Organisms. They were used to create an OA model by destabilization of the medial meniscus surgery (DMM) (n = 6 per group). Briefly, after the mice were anaesthetized, a medial articular incision was made to expose the leftjoint cavity, and then the tibial collateral ligament was transected. Finally, the articular incision was closed. In the control group, only the joint cavity was opened. One week after surgery, 1 mg/kg baicalein (MCE, HY-N0196) per knee, 1 mg/kg ML385 (MCE, HY-100523) per knee, 1 mg/kg AICAR (MCE, HY-13417) per knee or 1 mg/kg of the ferroptosis inhibitor ferrostatin-1 (Fer-1, MCE, HY-100579) was injected into the joint cavity of the mice once a week. Meanwhile, saline was injected into the control group. Mice were sacrificed after surgery 10 weeks.     Click to Show/Hide
Response Description	Baicalein alleviated osteoarthritis (OA) development by improving the activity of AMPKa/Nrf2/HO-1 signaling to inhibit chondrocyte ferroptosis, revealing baicalein to be a potential therapeutic strategy for OA. AMPKa preserved Nrf2 abundance in chondrocytes and promoted Nrf2 into nucleus by promoting Keap1 degradation

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[6]
Regulator for Ferroptosis	Driver
Responsed Drug	Astaxanthin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
In Vivo Model	6-week-Babl/c female mice were randomized to the following three groups of seven mice each: vehicle group, LPS group, Astaxanthin plus LPS group. Astaxanthin plus LPS group mice were pretreated with astaxanthin (20 mg/kg) byi.v injectionfor daily for 7 consecutive days. Astaxanthin was dissolved in 2%DMSO (vol/vol), 40% PEG-400 (vol/vol), 2% Tween 80 (vol/vol), and 56% PBS (vol/vol). On the last day, the mice were intraperitoneally injected with 5 mg/kg LPS or normal saline 2 h after the injection of astaxanthin. After 6 h of LPS stimulation, mice were euthanized to collect the BALF, and lung tissue samples. BALF was collected three times through a tracheal cannula with autoclaved normal saline, instilled up to a total volume of 1.8 ml.     Click to Show/Hide
Response Description	Astaxanthin protected LPS-induced cell inflammation and acute lung injury (ALI) in mice by inhibiting ferroptosis, and its effect was achieved through Keap1-Nrf2/HO-1 pathway. Therefore, our study indicates that ferroptosis will become a new target for the treatment of ALI, and astaxanthin is a potential drug for the treatment of ALI.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[7]
Regulator for Ferroptosis	Driver
Responsed Drug	Diethylhexylphthalate		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	HIF-1 signaling pathway			hsa04066
Cell Process	Cell ferroptosis
In Vitro Model	TM3 cells	Normal	Mus musculus	CVCL_4326
	TM4 cells	Normal	Mus musculus	CVCL_4327
In Vivo Model	Specific pathogen-free (SPF) pregnant C57BL/6 mice were purchased from the Experimental Animal Center of Chongqing Medical University. Under SPF conditions, all mice had free access to food and water. All mice were fed under a 12-hour light/dark cycle at 25 ± 2 , and the relative humidity was 50 ± 5%. Male neonatal mice were selected at postnatal day (PND) 21. Since we aimed to mimic the prepubertal testicular injury induced byDEHPexposure, all male mice were randomly divided into four groups and treated by oral gavage from PND22 to PND35 with corn oil (Aladdin, C116023, China), or DEHP at a dose of 100 mg/kg/day (D100), 250 mg/kg/day (D250), or 500 mg/kg/day (D500).     Click to Show/Hide
Response Description	Di-(2-ethylhexyl) phthalate (DEHP) exposure led to testicular injury including excessive ROS accumulation. Prepubertal DEHP exposure induces ferroptosis in mouse testes. In particular, MEHP exposure leads to ferroptosis in Leydig and Sertoli cells via the HIF-1/HO-1 signaling pathway.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[8]
Regulator for Ferroptosis	Suppressor
Responsed Drug	Iridin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hCMs (Human cardiomyocytes)
Response Description	Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[9]
Regulator for Ferroptosis	Driver
Responsed Drug	Ascorbic Acid		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	PaTu 8988t cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1847
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	mEFs (Mouse embryonic fibroblasts)
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In Vivo Model	All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 105 cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm3, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days.     Click to Show/Hide
Response Description	The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[10]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Ubiquitin mediated proteolysis			hsa04120
Cell Process	Cell ferroptosis
In Vitro Model	rSCs (Rat spinal cords)
In Vivo Model	Forty-eight adult female Sprague-Dawley rats weighing 200-220 g were purchased from Hunan SJA Laboratory Animal Co., Ltd. (Hunan, China) and divided into the following eight groups: sham (n = 6), SCI (n = 6), SCI + lentivirus (LV)-negative control 1 (NC1) (n = 6), SCI + LV-HMOX-1 (n = 6), SCI + LV-NC2 (n = 6), SCI + LV-USP7 (n = 6), SCI + LV-USP7 + sh-NC (n = 6), and SCI + LV-USP7 + sh-HMOX-1 (n = 6) groups. One week after animal adaptation and 30 min before operation, a subcutaneous injection of buprenorphine (0.05 mg/kg) was administered to the rats, along with inhalation of 5% isoflurane and an intraperitoneal injection of ketamine (75 mg/kg) and thiazide (10 mg/kg).     Click to Show/Hide
Response Description	In spinal cord injury (SCI) rats, USP7 directly bound to HMOX-1 and its overexpression promoted HMOX-1 expression via deubiquitination. To sum up, USP7 overexpression facilitated the expression of HMOX-1 through deubiquitination, thereby reducing ferroptosis and alleviating SCI.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[11]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
	Cell migration
	Cell invasion
In Vitro Model	H69 cells	Normal	Homo sapiens	CVCL_8121
	GBC-SD cells	Gallbladder carcinoma	Homo sapiens	CVCL_6903
Response Description	In vitro, gallbladder carcinoma (GBC) exhibited upregulated expression of TFAP2A, whose inhibition reduced GBC cell proliferation, migration, and invasion. Fe2+ and MDA levels were elevated. TFAP2A silencing attenuated the expression of key genes associated with oxidative stress such as heme oxygenase 1 (HO-1), nuclear factor erythroid 2 like 2 (Nrf2), ferritin heavy chain 1 (FTH1) and NAD(P)H quinone dehydrogenase 1 (NQO1).

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[12]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell autophagy
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
In Vivo Model	C57BL/6 mice (male, 10-15 weeks old) were food-deprived for 12 h before the procedures and were anesthetized with intraperitoneal injection of 1% sodium pentobarbital solution (40 mg/kg). Using a midline abdominal incision, bilateral renal IRI was induced by clamping renal pedicles for 30 min. After removal of the clamp, the kidneys were inspected to confirm reperfusion.     Click to Show/Hide
Response Description	Panx1 deletion induced the expression of a cytoprotective chaperone, heme oxygenase-1 (HO-1), and inhibited ferroptinophagy via the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. In summary, Panx1 deletion protects against renal ischemia/reperfusion injury (IRI) by attenuating MAPK/ERK activation in a ferroptotic pathway.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[13]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MRTEpiC (Mouse renal tubular epithelial cells)
	mRTECs (Mouse renal tubular epithelial cells)
	M4100-57 (Mouse renal tubular epithelial cells)
In Vivo Model	Gene knockout (Rev-erb-a-/-,Rev-erb-b-/-and icDKO) mice and wild-type littermates were treated with folic acid (i.p., 100 mg/kg, once daily for seven consecutive days) at ZT6 or ZT18 to induce acute kidney injury.     Click to Show/Hide
Response Description	Rev-erb-b (NR1D2) promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. Targeted inhibition of Rev-erb-b limits ferroptosis to ameliorate folic acid-induced acute kidney injury in mice.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[13]
Regulator for Ferroptosis	Driver
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	MRTEpiC (Mouse renal tubular epithelial cells)
	mRTECs (Mouse renal tubular epithelial cells)
	M4100-57 (Mouse renal tubular epithelial cells)
In Vivo Model	Gene knockout (Rev-erb-a-/-,Rev-erb-b-/-and icDKO) mice and wild-type littermates were treated with folic acid (i.p., 100 mg/kg, once daily for seven consecutive days) at ZT6 or ZT18 to induce acute kidney injury.     Click to Show/Hide
Response Description	Rev-erb-a (NR1D1) promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. Targeted inhibition of Rev-erb-a limits ferroptosis to ameliorate folic acid-induced acute kidney injury in mice.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[14]
Regulator for Ferroptosis	Driver
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	TCMK-1 cells	Normal	Mus musculus	CVCL_2772
In Vivo Model	C57BL/6 mice (male, 6-8 weeks old) were purchased from Guangdong Yaokang Biotechnology Co., Ltd. (China). According to a common sepsis protocol, we used the cecal ligation and puncture (CLP) method to construct a model of sepsis. For RNA sequencing, 5 mice were randomly divided into 2 groups: the CLP group (n = 3) and the sham group (n = 2). We anesthetized mice in the CLP group with 24% isoflurane. Under aseptic conditions, a 2-cm midline laparotomy was created below the diaphragm to expose the cecum. Two-thirds of the cecum was ligated with a 5-0 silk suture and punctured twice using a 22-gauge needle. The cecum was gently squeezed to extrude a small amount of feces through the perforation site. Animals were resuscitated with 1 mL of subcutaneous saline after CLP. The procedures of the sham group (controls) were the same as the CLP group, except for the ligation and perforation. The mice were sacrificed via neck fracture 6 hours after CLP, and the kidneys were taken for subsequent RNA sequencing.     Click to Show/Hide
Response Description	The mmu-miR-7212-5p-Hmox1 axis in ferroptosis and m6A RNA methylation regulators may have potential clinical significance for the future treatment of Sepsis-associated acute kidney injury (SA-AKI).

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[15]
Regulator for Ferroptosis	Driver
Responsed Drug	SP600125		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
Response Description	Following addition of the JNK (MAPK8) inhibitor SP600125, the expression of HO-1 decreased, expression of FTH1 was increased and iron accumulation was decreased. Therefore, it was hypothesized that NPs induced ferroptosis in BV2 cells via the JNK/HO-1/FTH1 pathway.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[16]
Regulator for Ferroptosis	Suppressor
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mPHs (Mouse primary hepatocytes)
In Vivo Model	In the adenovirus-mediated FGF21 over-expression mouse model, 12-week-old C57BL/6J male mice were divided into four groups: (1) EGFP vector overexpression + PBS injection group (n = 10), (2) EGFP vector overexpression + iron dextran injection group (n = 10), (3) FGF21-EGFP overexpression + PBS injection group (n = 10) and (4) FGF21-EGFP overexpression + iron dextran injection group (n = 10). The mice were administered PBS and iron dextran by intraperitoneal injection for 7 days.     Click to Show/Hide
Response Description	FGF21 could protect hepatocytes from developing iron overload-induced ferroptosis by stimulating HO-1 ubiquitination and subsequent degradation. The FGF21HO-1 pathway could be targeted for treating iron overload-induced ferroptosis-related diseases, particularly hereditary haemochromatosis (HH).

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[17]
Responsed Drug	Ferulic acid		Patented	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
In Vivo Model	Briefly, female BALB/c mice (6-8 weeks, weighing 20-25 g, purchased from Hunan SJA Laboratory Animal Co., Ltd., Changsha, Hunan, China) were raised in specific pathogen-free conditions under controlled temperature (23-25 ) and humidity (40-80%) as well as a 12 h dark/light cycle for 1 week of acclimation. They were fed a standard chow diet and waterad libitum. Mice were anaesthetised with 2% isoflurane inhalation and underwent moderate caecal ligation and puncture in accordance with a previously reported protocol (Rittirsch etal.2009). Meanwhile, mice in the control groups were subjected to a sham operation. Buprenorphin (0.05 mg/kg) was injected for postoperative analgesia, and all mice were placed in cages immediately after the surgical procedures with free access to water and food (Rittirsch etal. 2009).     Click to Show/Hide
Response Description	Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[18]
Responsed Drug	Dexmedetomidine		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mVTs (Mouse ventricular tissues)
In Vivo Model	A total of 32 male C57BL/6 mice (25 g, 8 weeks old) were obtained from the Guangdong Medical Lab Animal Center and housed in the Laboratory Animal Service Center (Jinan University, Guangdong, China). Mice were anesthetized with isoflurane (RWD Life Science) inhalation at the concentration of 2.5% for anesthetic induction and then at 1% for anesthetic maintenance until the end of the CLP. During the experiment, the body temperature was kept at 36-38 with a heating pad. Anesthetized mice were subjected to midline laparotomy. The cecum was carefully separated to avoid blood vessels damage and the cecum was identified and punctured twice with a 22-gauge needle. Then, the abdominal cavity was closed with two epithelium layers, followed by a normal saline injection subcutaneously for resuscitation before mice were returned to the cage.     Click to Show/Hide
Response Description	The attenuation of sepsisinduced HO1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dexmedetomidine alleviates sepsis induced myocardial cellular injury.

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[19]
Responsed Drug	Dihydroartemisinin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
In Vivo Model	All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days.     Click to Show/Hide
Response Description	Dihydroartemisinin could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[20]
Responsed Drug	Siramesine		Terminated	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Description	Lapatinib and siramesine was the most effective tyrosine kinase inhibitor and lysosome disruptor drug combination in inducing synergistic cell death in A549 and U87 cells. This cell death was through ferroptosis mediated by ROS and reduced expression of HO-1 in glioma cells.
Experiment 3 Reporting the Ferroptosis-centered Disease Response of This Regulator				[20]
Responsed Drug	Lapatinib		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Description	Lapatinib and siramesine was the most effective tyrosine kinase inhibitor and lysosome disruptor drug combination in inducing synergistic cell death in A549 and U87 cells. This cell death was through ferroptosis mediated by ROS and reduced expression of HO-1 in glioma cells.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[21]
Responsed Drug	Polygonatum cyrtonemaHua Polysaccharides		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
Response Description	Subsequent studies have revealed that Polygonatum cyrtonemaHua Polysaccharides (PCP) alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. PCP has the development potential as a new drug candidate for treating CNS diseases.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[22]
Responsed Drug	Honokiol		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-937 cells	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
	SKM-1 cells	Acute myeloid leukemia	Homo sapiens	CVCL_0098
Response Description	Honokiol decreased the viability of the targeted Acute myeloid leukemia cells, induced their cell cycle arrest at G0/G1 phase, and inhibited their colony-formation capacity. Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly. And HMOX1 was a critical target in honokiol-induced ferroptosis.

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[23]
Responsed Drug	3,5-bis((E)-2-fluorobenzylidene)piperidin-4-one hydrochloride		Investigative	Drug 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
	SAOS-2 cells	Osteosarcoma	Homo sapiens	CVCL_0548
Response Description	3,5-bis((E)-2-fluorobenzylidene)piperidin-4-one hydrochloride (EF24) upregulated HMOX1 to suppress GPX4 expression to induce ferroptosis by increasing MDA level, ROS level and intracellular ferric ion level. Thus, EF24 might serve as a potential agent for the treatment of HMOX1-positive osteosarcoma patients.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[24]
Responsed Drug	Zoledronic acid		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	MG-63 cells	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	MNNG/HOS Cl #5 cells	Osteosarcoma	Homo sapiens	CVCL_0439
Response Description	Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[25]
Responsed Drug	Cephalosporin		Approved	Drug Info
Pathway Response	Ferroptosis			hsa04216
	MAPK signaling pathway			hsa04010
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	XWLC-05 cells	Lung adenocarcinoma	Homo sapiens	CVCL_IQ71
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SGC-7901 cells	Gastric carcinoma	Homo sapiens	CVCL_0520
	CNE2 cells	Normal	Homo sapiens	CVCL_6889
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	ECV-304 cells	Bladder carcinoma	Homo sapiens	CVCL_2029
In Vivo Model	6-8 week old male balb/cnude micewere purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Nasopharyngeal carcinoma CNE2 cells were collected during logarithmic growth and rinsed with PBS twice and resuspended to a density of 1 x 107 cells/ml using fresh and cooled DMEM/F12 medium (free of FBS and antibiotics). Each mouse was inoculated subcutaneously with a 0.1 ml cell suspension on the right-side flank. Tumor-bearing mice were used for in vivo anticancer studies 8 days after inoculation when the average tumor volume reached ~200 mm3.     Click to Show/Hide
Response Description	Cephalosporin antibiotics showed highly specific and selective anticancer activity on nasopharyngeal carcinoma CNE2 cells both in vitro and vivo with minimal toxicity. Pathway analyses indicate apoptotic and the ErbB-MAPK-p53 signaling pathways are significantly enriched. HMOX1 represents the top one ranked upregulated gene by COS and overlaps with 16 of 42 enriched apoptotic signaling pathways. Inhibition of HMOX1 significantly reduced the anticancer efficacy of cefotaxime in CNE2 cells.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[26]
Responsed Drug	Carnosic acid		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Response Description	The current findings highlight that carnosic acid may re-sensitize cisplatin-resistant cells to cisplatin by inducing ferroptosis, which involves the inactivation of Nrf2/HO-1/xCT pathway. Hence, this research may support a promising therapeutic approach to overcome chemoresistance in Oral squamous cell carcinoma.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[27]
Responsed Drug	5-aminolevulinic acid		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	KYSE30 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	KYSE-510 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1354
	MKN45 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
In Vivo Model	KYSE30 cells were subcutaneously inoculated with 5 x 106 cells per site into both flanks on day 0. At 1 week after transplantation, tumor-bearing mice were randomly assigned to one of the following three groups: (1) saline as a control, (2) 10 mg/kg/day of 5-ALA, or (3) 30 mg/kg/day of 5-ALA. The treatment groups were orally administered 5-ALA once daily for 4 weeks, and the control group was orally administered saline during the same period.     Click to Show/Hide
Response Description	Modulation of GPX4 and HMOX1 by 5-aminolevulinic acid (5-ALA) induced ferroptosis in esophageal squamous cell carcinoma (ESCC). Furthermore, 5-ALA led to an increase in lipid peroxidation and exerted an antitumor effect in various cancer cell lines, which was inhibited by ferrostatin-1. Thus, 5-ALA could be a promising new therapeutic agent for ESCC.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[28]
Responsed Drug	Andrographis		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	MKN74 cells	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	NUGC-4 cells	Gastric signet ring cell adenocarcinoma	Homo sapiens	CVCL_3082
Response Description	Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM.

In total 4 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[29]
Responsed Drug	Propofol		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
In Vivo Model	CT26 (1 x 105 cells/100 uL) were injected into thetail veinof male BALB/c mice. Then the mice were randomly divided into saline, vehicle, propofol, and sevoflurane groups (n = 5 per group). Saline, fat emulsion (as vehicle control of propofol), and propofol (200 mg/kg) were intraperitoneally injected, while sevoflurane (1.8-2.0%) was administered by inhalation for 2 h. In another set of experiments, coloncancer cells (CT26 and HT29) were pretreated with two doses of propofol (5 ug/mL, 10 ug/mL) or fat emulsion (as vehicle control of propofol) in a cell culture medium for 2 h. After washing with phosphate-buffered saline (PBS), the cells were harvested,counted on a hemacytometer and prepared. Cells (CT26: 1 x 105 cells/100 uL, HT29: 1 x 106 cells/100 uL) were finnally injected into mice through the tail vein.Lung metastasiswas detected via hematoxylin and eosin staining (HE) or ex vivo bioluminescence imaging.     Click to Show/Hide
Response Description	Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting colorectal cancer cell metastasis through Nrf2-mediated ferroptosis inhibition.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[30]
Responsed Drug	Talaroconvolutin A		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	5 x 106 HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm3, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days.     Click to Show/Hide
Response Description	Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy.
Experiment 3 Reporting the Ferroptosis-centered Disease Response of This Regulator				[31]
Responsed Drug	tagitinin C		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
Response Description	Tagitinin C induces ferroptosis in colorectal cancer cells and has synergistic effect together with erastin. Mechanistically, tagitinin C induces ferroptosis through ER stress-mediated activation of PERK-Nrf2-HO-1 signaling pathway.
Experiment 4 Reporting the Ferroptosis-centered Disease Response of This Regulator				[32]
Responsed Drug	Andrographis		Approved	Drug Info
Pathway Response	Wnt signaling pathway			hsa04310
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In Vivo Model	Seven-week-old male athymic nude mice (Envigo, Houston, TX) were housed under controlled conditions of light and fed ad libitum. Approximately 5 x 106 parental and 5FUR HCT116 cells were suspended in the matrigel matrix (BD Biosciences, Franklin Lakes, NJ) and subcutaneously injected into mice using a 27-gauge needle (n = 10 per group). Mice were randomly assigned to different treatment groups and 5FU (30 mg/kg body weight) or andrographis (125 mg/kg body weight) or their combination were given intraperitoneally on alternative days for up to 15 days.     Click to Show/Hide
Response Description	Combined treatment with andrographis was significantly more effective than 5FU and andrographis alone and that these effects were in part orchestrated through dysregulated expression of key genes (including HMOX1, GCLC, GCLM and TCF7L2) within the ferroptosis and Wnt-signaling pathways. Andrographis might offer a safe and inexpensive adjunctive therapeutic option in the management of colorectal cancer patients.

In total 2 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[33]
Responsed Drug	Haloperidol		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Description	The study demonstrated that haloperidol strengthened sorafenib-induced ferroptosis in Hepatocellular carcinoma cell lines for the first time. During ferroptosis, haloperidol substantially increased the cellular levels of Fe2+, GSH and lipid peroxidation. Additionally, haloperidol induced the expression of HO-1.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[34]
Responsed Drug	Eupalinolide B		Investigative	Drug Info
Pathway Response	MAPK signaling pathway			hsa04010
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell migration
	Cell proliferation
In Vitro Model	SMMC-7721 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In Vivo Model	Four-week-old nude mice (BALB/c) were used, and they were housed for 1 week in a specific pathogen-free (SPF) environment before experimentation. Each mouse received subcutaneous injections of 1 x 106 SMMC-7721 or HCCLM3 cells in 200 uL phosphate-buffered saline (PBS) into both flanks. One group was intraperitoneally injected every two days with EB at 25 or 50 mg/mouse body weight, for a total of 3 weeks. As a control, DMSO was used in another group. Tumor size was measured to calculate tumor volume, and mouse body weights were monitored every two days.     Click to Show/Hide
Response Description	Eupalinolide B (EB) exerts anti-proliferative activity in hepatic carcinoma by blocking cell cycle arrest at S phase and inducing ferroptosis mediated by endoplasmic reticulum (ER) stress, as well as HO-1 activation. And EB has the ability to inhibit cell proliferation and migration in hepatic carcinoma.

In total 4 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[35]
Responsed Drug	Ginkgetin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	SPC-A1 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In Vivo Model	Briefly, when tumours on transplanted nude mice reached around 100 mm3, the mice were randomized divided into eight groups: control, ginkgetin, DDP, ginkgetin + DDP, UAMC 3203, ginkgetin + UAMC 3203, DDP + UAMC 3203, ginkgetin + DDP + UAMC 3203. Both DDP (3 mg/kg) and ginkgetin (30 mg/kg) were administered by intraperitoneal injection, with 2 - 3 times per week and once per day, respectively. UAMC 3203 (10 mg/kg) was administered 5 days/week by intraperitoneally injection. Tumour size and body weight were measured 3 times per week. After dosing 31 days, the nude mice were sacrificed, and tumours were removed and weighed.     Click to Show/Hide
Response Description	The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured non-small cell lung cancer (NSCLC) cells.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[36]
Responsed Drug	Gefitinib		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
In Vivo Model	Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5.     Click to Show/Hide
Response Description	The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells.
Experiment 3 Reporting the Ferroptosis-centered Disease Response of This Regulator				[36]
Responsed Drug	Betulin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
In Vivo Model	Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5.     Click to Show/Hide
Response Description	The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells.
Experiment 4 Reporting the Ferroptosis-centered Disease Response of This Regulator				[37]
Responsed Drug	S-3'-hydroxy-7', 2', 4'-trimethoxyisoxane		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
In Vivo Model	When tumor volumes in xenograft nude mice reached an average of roughly 100 mm3, the mice were randomly divided into 3 groups of 6 mice each: control, ShtIX, and ShtIX + Fer-1. The treated group received ShtIX or ShtIX combined with Fer-1 injections into the tail vein of the mice every three days for 7 times, whereas the control group received saline. Every four days, the volume and weight of the tumors were measured. As soon as the test was completed, the nude mice were slaughtered, and the tumor tissues were retrieved. The in vivo experiments were approved by the Animal Care and Use Committee of Hainan Medical College and following the animal rules.     Click to Show/Hide
Response Description	S-3'-hydroxy-7', 2', 4'-trimethoxyisoxane (ShtIX) caused ferroptosis in Non-small cell lung cancer (NSCLC) cells, and inhibiting the Nrf2/HO-1 pathway can considerably exacerbate the effect of ShtIX-induced ferroptosis.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[38]
Responsed Drug	Shuganning injection		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	SK-BR-3 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-468 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	BT-549 cells	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MCF-10A cells	Normal	Homo sapiens	CVCL_0598
	786-O cells	Renal cell carcinoma	Homo sapiens	CVCL_1051
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	WPMY-1 cells	Normal	Homo sapiens	CVCL_3814
	U-87MG cells	Glioblastoma	Homo sapiens	CVCL_0022
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
In Vivo Model	MDA-MB-231 cells resuspended in PBS (2 x 106/100 m1) were injected subcutaneously into bothhind limbsof 4-6 weeks old femalenude mice. A week later, SGNI was administrated byintraperitoneal injectionat a dose of 112.5 mg/kg/3 d.     Click to Show/Hide
Response Description	Shuganning injection (SGNI) induced a ferroptotic cell death of Triple-negative breast cancer (TNBC) cells. Mechanistically, SGNI induced ferroptosis was dependent on HO-1, which promotes intracellular labile iron pool accumulation, and was alleviated by HO-1 knockdown and inhibition by tin protoporphyrin IX.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[39]
Responsed Drug	Norcantharidin		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
In Vivo Model	Athymic nu/nu female mice aged 6-8 weeks (n = 9; mean weight, 20.21 ± 1.54 g) were purchased from the specific pathogen SPF (Beijing) Lab Animals Technology Co. Ltd. Mice were housed in a temperature- and humidity-controlled environment (20-24 , 45-55% humidity), with free access to food and water and in groups of three. All procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC ID: 17-3256) at Nantong University and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals.     Click to Show/Hide
Response Description	Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following norcantharidin (NCTD) treatment. Collectively, NCTD may represent a potent anticancer agent in ovarian cancer cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/ HO-1/GPX4/xCT axis.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[40]
Responsed Drug	Juglone		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell migration
In Vitro Model	Ishikawa cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
Response Description	Juglone as a natural quinone from C. cathayensisgreen peel could exert its anti-cancer activity by inducing iron dependent autophagy and inhibiting the migration of endometrial cancer (EC) cells. Subsequently, Fe2+ accumulation, lipid peroxidation, GSH depletion, the upregulation of HMOX1, and heme degradation to Fe2+ were reported. Juglone was involved in inducing autophagy and inhibiting cell migration and endoplasmic reticulum stress.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[41]
Responsed Drug	Isothiocyanate-containing hybrid AR antagonist 13		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Glutathione metabolism			hsa00480
Cell Process	Cell ferroptosis
In Vitro Model	VCaP cells	Prostate carcinoma	Homo sapiens	CVCL_2235
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
	LNCaP C4-2 cells	Prostate carcinoma	Homo sapiens	CVCL_4782
	22Rv1 cells	Prostate carcinoma	Homo sapiens	CVCL_1045
	RWPE-1 cells	Normal	Homo sapiens	CVCL_3791
	MDA-kb2 cells	Breast adenocarcinoma	Homo sapiens	CVCL_6421
Response Description	ITC-ARi 13 and buthionine sulfoximine (BSO) cooperatively downregulate AR and induce ferroptosis likely through increasing the accessibility of 13/12b to cellular targets, escalating free intracellular ferrous iron and attenuating GSH-centered cellular defense and adaptation. Further studies on the combination of ITC-ARi and GSH synthesis inhibitor could result in a new modality against castration-resistant prostate cancer (CRPC). Collectively, the combination of ITC-ARi 13 and BSO reveals a pro-ferroptotic role of Nrf2 through upregulating HO-1 under GSH-deficient conditions.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[42]
Responsed Drug	Curcumin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	Nthy-ori3-1 cells	Normal	Homo sapiens	CVCL_2659
	Nthy-ori3-1 cells	Normal	Homo sapiens	CVCL_2659
	FTC 238 cells	Thyroid gland follicular carcinoma	Homo sapiens	CVCL_2447
Response Description	Knockdown of HO-1 inhibits ferroptosis by upregulating the GPX4 expression in follicular thyroid cancer cells. We conclude that curcumin inhibits the tumorigenesis of follicular thyroid cancer via HO-1-induced activation of the ferroptosis signalling pathway.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[43]
Responsed Drug	Cadmium		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	TM3 cells	Normal	Mus musculus	CVCL_4326
In Vivo Model	Eight-week-old adult male C57BL/6J mice were raised for 7 days before the study in a temperature and humidity controlled animal facility (22-25 , 50% relative humidity) with a12-h light/dark cycles. A total of 10 mice were randomly assigned into two groups. As described in our previous study, the control group was treated with 0.9% NaCl (0 mg CdCl2), and the treatment group was intraperitoneally injected with CdCl2 at a dose of 1.0 mg per kg of body weight for 1 week.     Click to Show/Hide
Response Description	Cadmium induced ferroptosis by iron homeostasis dysregulation, mediated by excessive activation of HMOX-1. The disruption of autophagy flow contributed to Cd-induced testicular dysfunction and attenuated testosterone synthesis.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[44]
Responsed Drug	Gastrodin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	C6 cells	Malignant glioma	Rattus norvegicus	CVCL_0194
Response Description	Gastrodin induced GPX4, Nrf2 and HO-1 expression to protect C6 cells from H2O2-induced ferroptosis. Gastrodin pretreatment effectively reduced H2O2-induced oxidative damage, indicating gastrodin is a potential antioxidant that reduced cytotoxic ROS. The role of gastrodin in ferroptosis presents a new perspective for understanding parkinson's disease.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[45]
Responsed Drug	Salidroside		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
In Vivo Model	B6.1291-Nfe2l2tm1Ywk/J (Nrf2-/-mice, 017009)and wild-type C57BL/6 were originally from the Jackson Laboratory. Grouping and administration were started when weighing approximately 28-33 g. All mice were housed in a laboratory environment with free access to adequate food and water under a 12 h/12 h light/dark cycle at 22 ± 1 and 55 ± 5% humidity. All procedures conformed to the protocols of the Animal Welfare Commission and Ethical Committee of Southern Medical University. The Nrf2-/- mice were identified by genotyping as shown in Fig.1B. WT and Nrf2-/- mice were randomly assigned to 32 groups (3 groups for WT mice and 3 groups for Nrf2-/- mice) as follows: a sham group, sham + Ab1-42 group, and Salidroside + Ab1-42 group.     Click to Show/Hide
Response Description	Salidroside plays a neuroprotective role by inhibiting neuronal ferroptosis in A1-42-induced Alzheimer's disease mice and Glu-injured HT22 cells, and its mechanism is related to activation of the Nrf2/HO1 signaling pathway.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[46]
Responsed Drug	Astragaloside IV		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	SAH model was constructed by applying endovascular perforation in the rats, according to the protocol introduced in a previous study (Wei et al., 2020), except for slight modifications. Briefly, after performing intraperitoneal anesthesia with 40 mg/kg sodium pentobarbital, the right common carotid, external and internal carotid arteries of the rats were exposed and isolated. The right external carotid artery was ligated, and a 4-0 single-strand nylon thread was used to insert the right internal carotid artery through the stump of the external carotid artery and the bifurcation of the common carotid artery. When resistance is felt when the suture enters the intracranial segment, proceed approximately 3 mm to penetrate internal carotid artery at the bifurcation of middle cerebral artery. The suture was held in this position for 10 s and was then withdrawn. The rats in the Sham group went through an identical procedure, without the suture at the point of resistance. Throughout the experiment, the body temperature of the rats was sustained at around 37 by using a thermal blanket. After the wounds were sutured, the rats were placed in a separate cage and neurological function was closely observed.     Click to Show/Hide
Response Description	Astragaloside IV (AS-IV) triggered Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of subarachnoid hemorrhage (SAH). The Nrf2 inhibitor ML385 blocked the beneficial effects of neuroprotection. These results consistently suggest that ferroptosis is profoundly implicated in facilitating EBI in SAH, and that AS-IV thwarts the process of ferroptosis in SAH by activating Nrf2/HO-1 pathway.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[47]
Responsed Drug	Caryophyllene		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	rPAs (Rat primary astrocytes)
In Vivo Model	Rats were anesthetized withisoflurane(2-3% oxygen) and placed in asupine position. And theright common carotid artery (CCA),external carotid artery (ECA), andinternal carotid artery (ICA) were exposed in sequence and separated carefully. Then we ligated the CCA and the ECA in turn, and at the same time, we clamped the internal carotid artery with an arterial clamp. Finally, we inserted a silicone nylon monofilament from the CCA into themiddle cerebral arteryand temporarily fixed it. After 1.5 h ofischemia, the monofilament was taken out and the blood vessels were ligated at theincision. The neck wound was sutured with surgical sutures. Subsequent experiments were performed after 12 h ofreperfusion. In thesham operationrats, except for the absence of the monofilament, the sham operation rats underwent the same surgical procedures as the MCAO/R model rats.     Click to Show/Hide
Response Description	Our results indicated the critical role of ferroptosis in cerebral ischemia reperfusion injury. For the first time, we showed that the significant neuroprotective effects of b-Caryophyllene (BCP) in attenuating ischemic stroke injury are correlated with ferroptosis regulation, and its mechanism is associated with activation of the NRF2/HO-1 axis.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[48]
Responsed Drug	Astragaloside IV		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	1% sodium pentobarbital (40 mg/kg) was administered to the rats intraperitoneally to anesthetize them before placing them in a brain stereotaxic device. An incision was created in the midline of the neck to expose the common internal and external carotid arteries. After ligating and cutting the external carotid artery on the left side, a 3-mm stump was exposed. We then perforated the carotid artery at the bifurcation of the middle and anterior cerebral arteries utilizing an 18-20-mm-long surgical filament (0.26 mm diameter; Beijing Cinontech Co. Ltd., China) was threaded through the external carotid artery stump into the internal carotid artery and left in situ for 120 min. After that, the filament was withdrawn to facilitate reperfusion. Rats in the sham surgery group received the identical procedure as the other rats but without filament insertion.     Click to Show/Hide
Response Description	Astragaloside IV (AS-IV) administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-, interleukin-1 (IL-1), IL-6, and NF-B, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[49]
Responsed Drug	ADA-409-052		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
	Neuro-2a cells	Neuroblastoma	Mus musculus	CVCL_0470
	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
In Vivo Model	Brain penetration study was carried out by TCG Lifesciences Ltd (Kolkata, India) in male BALB/c mice (6-8 weeks old; 18-20 g, in-house breeding). Mice were housed individually under 12/12 h lightdark cycle with free access to food and water. In two experiments 10 mg/kg or 30 mg/kg of ADA-409-052 (HPLC Purity: 99.7%) dissolved in Tween-80 (0.5%, Merck, Germany) -methylcellulose (Sigma) solution was administered as a single bolus by oral gavage (p.o.). ADA-409-052- or vehicle-administered mice were sacrificed 0.75, 4, and 24 h later (n = 3/group).     Click to Show/Hide
Response Description	ADA-409-052 inhibits tert-Butyl hydroperoxide (TBHP)-induced lipid peroxidation (LP) and protects against ferroptotic cell death triggered by glutathione (GSH) depletion or glutathione peroxidase 4 (GPx4) inhibition in neuronal cell lines. Moreover, ADA-409-052 efficiently reduces infarct volume, edema and expression of pro-inflammatory genes in a mouse model of thromboembolic stroke. In addition, ADA-409-052 reduced the expression of stroke-induced Hmox1.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[50]
Responsed Drug	Gastrodin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
Response Description	Gastrodin (GAS) is a component of Gastrodia elata Blume, with strong antioxidant activity in neurodegenerative diseases. GAS increased the nuclear translocation of Nrf2, up-regulated the downstream HO-1 protein expression in HT-22 cells following treatment with glutamate.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[51]
Responsed Drug	Sodium iodate		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	ARPE-19 cells	Normal	Homo sapiens	CVCL_0145
In Vivo Model	In this study, sixteen-week-old male C57BL/6 mice were used and housed in a standard laboratory environment. Forin vivostudies, left eyes were pretreated with a single intravitreal injection of DMSO (1 uL) or 1X PBS (1 uL), and right eyes were pretreated with Fer-1 (30 uM, a single intravitreal injection, 1 uL), DFO (100 uM, a single intravitreal injection, 1 uL), or ZnPP (50 mg/kg, intraperitoneal injection once a week). 15 min later, injection of NaIO3(35 mg/kg, a single injectionviatail vein), or 1X PBS (a single injectionviatail vein, 75 uL) has been performed. After 2 weeks, mice were used for subsequent experiments.     Click to Show/Hide
Response Description	Sodium iodate-induced oxidative stress model has been identified to be heme oxygenase-1 (HO-1)-regulated ferroptosis, which is controlled by the Nrf2-SLC7A11-HO-1 hierarchy. These findings highlight that targeting HO-1-mediated RPE ferroptosis could serve as an effectively retinal-protective strategy for retinal degenerative diseases prevention, including age-related macular degeneration (AMD).

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[52]
Responsed Drug	Curcumin		Investigative	Drug 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	Two-month-old male New Zealand rabbits purchased from the Medical Experimental Animal Center of Bengbu Medical College were used as experimental subjects. Streptozotocin was dissolved in sterile saline and intraperitoneally injected into the rabbits at a dose of 80 mg/kg. The rabbits were allowed to eat freely after receiving the injection. The fasting blood glucose levels of the rabbits were monitored regularly. The diabetic rabbit model was considered successfully established when the fasting blood glucose level was measured as 11 mmol/L twice or 14 mmol/L once. Following successful modelling, grouping was performed as follows: blank control group (Con-Group), diabetic rabbit group (DM-Group), diabetic rabbit + every other day curcumin administration group (Qod-Group), and diabetic rabbit + daily administration group (Qd-Group).     Click to Show/Hide
Response Description	Curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy.

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[53]
Responsed Drug	Iridin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
In Vivo Model	In vivo, the LIRI model was established as described earlier. All mice were anesthetized with pentobarbital administered intraperitoneally (50 mg/kg, Sigma-Aldrich, MO, USA). After endotracheal intubation, the mice were ventilated using a rodent ventilator (MiniVent, Harvard Apparatus, USA), with the title volume set to 7 ml/kg, the respiratory rate set to 120 times/min, and the inspiratory/expiratory ratio set to 1: 2. A noninvasive clamp was used to interrupt the left pulmonary hilum, causing lung ischemia. The clamp was released after 60 minutes of ischemia, and the left lung was reperfused for 120 minutes. Animals were euthanized via cervical dislocation at the end of the experiment. Following that, lung specimens and bronchoalveolar lavage fluid were harvested for analysis. All procedures except lung ischemia were performed on mice in the sham group.     Click to Show/Hide
Response Description	As a result, irisin postconditioning may protect against lung I/R damage by suppressing ferroptosis via the Nrf2/HO-1 signaling axis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[54]
Responsed Drug	Apigenin		Investigative	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HUVECs (Human umbilical vein endothelial cells)
In Vivo Model	Mice were exposed to 12/12 h of light/darkness and given free access to food and water. All C57BL/6J mice were fasted for 12 h and anesthetized by intraperitoneal injection of 1% sodium pentobarbital before modeling. Later, the superior mesenteric artery (SMA) was subjected to 45 min of global no-flow ischemia, followed by 90 min of reperfusion to induce IIRI. The successful model could be revealed by the microcirculation detector. In order to investigate the effects of APG, mice were randomly divided into different groups: Sham group, IIRI group, APG groups (2 mg/kg, 4 mg/kg and 8 mg/kg), ZnPPIX group (Protoporphyrin Zinc(), Dalian Meilun Biotech Co., Ltd., China, 10mg/kg), Selegiline group (10 mg/kg, Shandong Topscience Biotech Co., Ltd., China) and the ZnPPIX + Selegiline group (10 mg/kg ZnPPIX and 10 mg/kg Selegiline). As mentioned above, drug was intraperitoneal injected after a 10-min-ischemia.     Click to Show/Hide
Response Description	MST analysis suggested that Apigenin could specifically bind to heme oxygenase 1 (HO-1) and monoamine oxidase b (MAO-B). Simultaneously, APG could attenuate ROS generation and Fe2+ accumulation, maintain mitochondria function thus inhibit ferroptosis and alleviate intestinal ischemia-reperfusion injury.
Experiment 3 Reporting the Ferroptosis-centered Disease Response of This Regulator				[55]
Responsed Drug	Dimethyl fumarate		Approved	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	AML12 cells	Normal	Mus musculus	CVCL_0140
In Vivo Model	The mice were randomly divided into four groups of six: sham + vehicle, sham + DMF, IR + vehicle, and IR + DMF. The mice were supplemented with DMF at a concentration of 100 mg/kg or DMSO by daily oral gavage for a week before surgery, as previously reported. As stated in a prior study, the partial warm liver IRI model was developed. Briefly, the sham group only had free hepatic portal blood vessels after laparotomy, and the blood flow was not obstructed. As for the hepatic IR group, the blood supply to the left and mid-hepatic lobes was blocked, resulting in 70% mouse liver IRI for 90 min. The mice were put on a heated blanket after surgery in order to maintain body temperature and monitor vital signs. Blood supply was restored for 6 h. Died mice were eliminated for testing prior to sample collection. The mice were euthanized after the sample were obtained. The same experimenter carried out all surgeries.     Click to Show/Hide
Response Description	NRF2 knockdown notably decreased the expression of SLC7A11 and HO-1 and blocked the anti-ferroptosis effects of dimethyl fumarate (DMF). DMF inhibits ferroptosis by activating the NRF2/SLC7A11/HO-1 axis and exerts a protective effect against hepatic ischemia-reperfusion injury.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[56]
Responsed Drug	Ginsenoside Rg3		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	AR42J cells	Digestive system neoplasms	Rattus norvegicus	CVCL_0143
In Vivo Model	Male C57BL/6 mice (8 weeks old; SPF; weighing 24-26 g, n = 16 in total) were purchased from SPF (Beijing) Biotechnology Co., Ltd. All mice were housed in an environmentally controlled room at a temperature ranging from 20 to 24 on a 12 h light/dark cycle and used in the experiments following an overnight fast with water, availablead libitum. All procedures followed the Principles of Laboratory Animal Care (NIH publication number 85Y23, revised in 1996), and the experimental protocol was approved by the Animal Care Committee, Nanjing Medical University (NMU-2021JK-085).     Click to Show/Hide
Response Description	Taken together, the present study, to the best of our knowledge, is the first to reveal a protective role for Ginsenoside Rg3 in mice with acute pancreatitis by suppressing oxidative stressrelated ferroptosis and the activation of the NRF2/HO1 pathway.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[57]
Responsed Drug	Dioscin		Preclinical	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
In Vivo Model	Six-week-old male Wistar rats (170-200 g) were obtained from Changsheng Biotechnology Co., Ltd. (Changchun, China), and all of them were fed under SPF-conditions. The rats were acclimatized to natural light/dark cycles at a controlled temperature of 22 + 2 with free access to food and water. The experiment was comprised of four groups: the C group (0.5% carboxymethyl cellulose sodium [CMC-Na], n = 6); the Dio group (dioscin-treated rats, n = 6); the CP group (cisplatin-treated mice, n = 6); and the Dio + CP group (dioscin plus cisplatin-treated rats, n = 6). Rats were gavaged with dioscin (60 mg/kg) for ten days, and cisplatin (10 mg/kg) was intraperitoneally injected once on the seventh day.     Click to Show/Hide
Response Description	Dioscin exerts a reno-protective effect by decreasing renal oxidative injury, apoptosis and ferroptosis through the Nrf2/HO-1 signaling pathway, providing a new insight into acute kidney injury prevention.

In total 1 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[58]
Responsed Drug	Sevoflurane		Approved	Drug Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
In Vivo Model	Male C57BL/6 mice (8 weeks, 23-25 g) were obtained from Beijing Hua Fu Kang Biotechnology Co. LTD (Beijing, China). A total of 96 mice were randomly divided into 6 groups (n = 16 per group): Sham group, LPS group, Fer-1 group, Fe group, Sev group, and Fe + Sev group. Mice were given 5 mg/kg LPS intranasally to construct LPS-induced ALI model. To study the role of ferroptosis in ALI, the mice in the Fer-1 or Fe groups were administered with Fer-1 (0.8 mg/kg; Ferrostatin-1, the inhibitor of ferroptosis) or Fe (8 mg/kg; Fe-citrate (III), ferroptosis inducer) via tail vein injection once a day for 3 consecutive days before treatment with LPS, respectively. To study the effect of Sev on ALI mice, the mice in Sev group were treated with LPS for 2 h, and then Sev, delivered by gaseous admixture (oxygen) at a concentration of 3% via a calibrated vaporizer, was administered via an endotracheal tube for 4 h. In order to study the effect of Sev on ferroptosis, the mice in Fe + Sev group were administered with Fe via tail vein injection once a day for 3 consecutive days, and then treated with LPS and Sev. Sham group was given 0.9% NaCl (containing 0.1% DMSO).     Click to Show/Hide
Response Description	Sevoflurane (Sev) could eliminate the worsening effects of ferroptosis inducer Fe-citrate on LPS-induced acute lung injury (ALI) to a certain extent. Sev inhibited ferroptosis by up-regulating HO-1 expression to reduce LPS-induced ALI, which may provide a possible mechanism for the application of Sev in clinical anesthesia.

In total 3 item(s) under this disease				Disease Info
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator				[59]
Responsed Drug	Astaxanthin		Investigative	Drug Info
Pathway Response	NF-kappa B signaling pathway			hsa04064
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell apoptosis
In Vitro Model	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In Vivo Model	Mice were randomly divided into four groups as follows (n = 5): (1) control, (2) APAP (MCE, Monmouth Junction, NJ, USA), (3) olive oil + APAP (oil + APAP), and (4) ASX (Energy Chemical, Shanghai, China) dissolved in olive oil + APAP (ASX + APAP). Astaxanthin was dissolved in olive oil to obtain a mixture of 20 mg/mL. Mice in groups 3 and 4 were given a dose of olive oil and a mixture of 5 mL/kgBW by gavage every day for 2 weeks. On day 15, mice in groups 2, 3, and 4 were given a peritoneal injection of 500 mg/kg APAP to induce liver injury. The mice were fasted for 12 h before the administration of APAP. Ten hours after APAP administration, blood and liver tissue were collected for further examination and analyses. Blood was centrifuged to obtain supernatants,which were stored at -80. Liver tissues were immediately removed from each animal, and homogenates were processed with formaldehyde and glutaraldehyde for protein and histological analysis.     Click to Show/Hide
Response Description	Astaxanthin reduced inflammation through the NF-B pathway, inhibited oxidative stress and ferroptosis, and increased autophagy through the Nrf2/HO-1 pathway, ameliorating acetaminophen-induced liver injury in vivo and in vitro.
Experiment 2 Reporting the Ferroptosis-centered Disease Response of This Regulator				[2]
Responsed Drug	Ulinastatin		Phase 3	Drug Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In Vivo Model	Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection.     Click to Show/Hide
Response Description	Ulinastatin plays a role in mitigation of APAP-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression.
Experiment 3 Reporting the Ferroptosis-centered Disease Response of This Regulator				[60]
Responsed Drug	Abietic acid		Investigative	Drug Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	AML12 cells	Normal	Mus musculus	CVCL_0140
In Vivo Model	APAP-induced liver injury model was induced byintraperitoneal injection 300 mg/kg APAP. The mice of APAP + abietic acid (10, 20, 40 mg/kg) were given abietic acid by intraperitoneal injection 1 h before APAP treatment. The doses of abietic acid used in this study were based on previous studies. Twelve hours later, the mice were sacrificed after anesthesia with 1%pentobarbital (50 mg/kg) injected intraperitoneally and the samples were collected.     Click to Show/Hide
Response Description	APAP could increase malondialdehyde (MDA) and Fe2+ levels, and decrease ATP and glutathione (GSH) levels, as well as glutathione peroxidase 4 (GPX4) and xCT expression. However, these changes induced by APAP were prevented by abietic acid, indicating abietic acid could inhibit APAP-induced ferroptosis. Furthermore, abietic acid inhibited APAP-induced liver injury, NF-B activation and increased the expression of Nrf2 and HO-1.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[1]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Supraventricular tachycardia [ICD-11: BC81]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HL-1 cells	Normal	Mus musculus	CVCL_0303
In Vivo Model	Adult male mice (C57BL6) aged 12 weeks were purchased from HUAFUKANG Bioscience Co, Ltd (Beijing, China) and housed in controlled temperature with free access to water and standard pellet chow. The animal studies were approved by the General Hospital of Northern Theatre Command Animal Care Committee. All experiments were carried out in accordance with institutional regulations and in adherence with the Guide for the Care and Use of Laboratory Animals issued by the US National Institutes of Health (NIH Publication, 8th Edition, 2011). Additionally, the study was reported in accordance with ARRIVE guidelines. After an accommodation period of 7 days, the mice were randomly assigned into the following groups (n = 18/group): control group, control + Ferrostatin-1 (Fer-1)/Erastin/EX527 group, ethanol (EtOH) group, EtOH + Fer-1 group, EtOH + Icar group, EtOH + Icar + Erastin group, EtOH + Icar + EX527 group.     Click to Show/Hide
Response Description	Icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to atrial fibrillation.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[2]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Injury of intra-abdominal organs [ICD-11: NB91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In Vivo Model	Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection.     Click to Show/Hide
Response Description	Ulinastatin (UT1) plays a role in mitigation of Acetaminophen (APAP)-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[3]
Regulator for Ferroptosis	Driver
Responsed Disease	Multiple myeloma [ICD-11: 2A83]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	RPMI-8226 cells	Plasma cell myeloma	Homo sapiens	CVCL_0014
	U266B1 cells	Plasma cell myeloma	Homo sapiens	CVCL_0566
	AML12 cells	Normal	Mus musculus	CVCL_0140
Response Description	Andrographolide (Andro) may block the Nrf2/HO-1 signaling pathway by activating P38 ( MAPK14), thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in Multiple myeloma (MM) cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[4]
Regulator for Ferroptosis	Driver
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	DLD-1 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0248
	LoVo cells	Colon adenocarcinoma	Homo sapiens	CVCL_0399
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In Vivo Model	The DLD-1 cell suspension (4 x 106 cells/200 ul) was injected subcutaneously into the right dorsal flank of 5-week-old male BALB/c nude mice (Charles River, China). The mice were randomly divided into four groups (5 mice/group): 1) the control group, 2) the RSL3 group, 3) the cetuximab group, and 4) the RSL3 + cetuximab group. Both RSL3 (5 mg/kg) and cetuximab (13 mg/kg) were administered by intraperitoneal injection in a volume of 100 ul once per day. The tumour volume was calculated as 0.5 x length x width2. After 17 days of treatment, the mice were sacrificed, and the tumours were removed. Then, tumour tissue obtained from the different treated groups was subjected to western blotting and immunohistochemical experiments.     Click to Show/Hide
Response Description	Our work reveals that cetuximab enhances the cytotoxic effect of RSL3 on KRAS mutant Colorectal cancer (CRC) cells and that cetuximab enhances RSL3-induced ferroptosis by inhibiting the Nrf2/HO-1 axis through the activation of p38 MAPK.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[5]
Regulator for Ferroptosis	Driver
Responsed Disease	Degenerative arthritis [ICD-11: FA05]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hCDs (Chondrocytes)
In Vivo Model	C57BL/6J (WT) mice (8 weeks old, male) were purchased from Nanjing Medical university, and AMPK-KO mice were purchased from Shanghai Model Organisms. They were used to create an OA model by destabilization of the medial meniscus surgery (DMM) (n = 6 per group). Briefly, after the mice were anaesthetized, a medial articular incision was made to expose the leftjoint cavity, and then the tibial collateral ligament was transected. Finally, the articular incision was closed. In the control group, only the joint cavity was opened. One week after surgery, 1 mg/kg baicalein (MCE, HY-N0196) per knee, 1 mg/kg ML385 (MCE, HY-100523) per knee, 1 mg/kg AICAR (MCE, HY-13417) per knee or 1 mg/kg of the ferroptosis inhibitor ferrostatin-1 (Fer-1, MCE, HY-100579) was injected into the joint cavity of the mice once a week. Meanwhile, saline was injected into the control group. Mice were sacrificed after surgery 10 weeks.     Click to Show/Hide
Response Description	Baicalein alleviated osteoarthritis (OA) development by improving the activity of AMPKa/Nrf2/HO-1 signaling to inhibit chondrocyte ferroptosis, revealing baicalein to be a potential therapeutic strategy for OA. AMPKa preserved Nrf2 abundance in chondrocytes and promoted Nrf2 into nucleus by promoting Keap1 degradation

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[6]
Regulator for Ferroptosis	Driver
Responsed Disease	Lung injury [ICD-11: NB32]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
In Vivo Model	6-week-Babl/c female mice were randomized to the following three groups of seven mice each: vehicle group, LPS group, Astaxanthin plus LPS group. Astaxanthin plus LPS group mice were pretreated with astaxanthin (20 mg/kg) byi.v injectionfor daily for 7 consecutive days. Astaxanthin was dissolved in 2%DMSO (vol/vol), 40% PEG-400 (vol/vol), 2% Tween 80 (vol/vol), and 56% PBS (vol/vol). On the last day, the mice were intraperitoneally injected with 5 mg/kg LPS or normal saline 2 h after the injection of astaxanthin. After 6 h of LPS stimulation, mice were euthanized to collect the BALF, and lung tissue samples. BALF was collected three times through a tracheal cannula with autoclaved normal saline, instilled up to a total volume of 1.8 ml.     Click to Show/Hide
Response Description	Astaxanthin protected LPS-induced cell inflammation and acute lung injury (ALI) in mice by inhibiting ferroptosis, and its effect was achieved through Keap1-Nrf2/HO-1 pathway. Therefore, our study indicates that ferroptosis will become a new target for the treatment of ALI, and astaxanthin is a potential drug for the treatment of ALI.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[7]
Regulator for Ferroptosis	Driver
Responsed Disease	Testicular injury [ICD-11: NB9Z]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	HIF-1 signaling pathway			hsa04066
Cell Process	Cell ferroptosis
In Vitro Model	TM3 cells	Normal	Mus musculus	CVCL_4326
	TM4 cells	Normal	Mus musculus	CVCL_4327
In Vivo Model	Specific pathogen-free (SPF) pregnant C57BL/6 mice were purchased from the Experimental Animal Center of Chongqing Medical University. Under SPF conditions, all mice had free access to food and water. All mice were fed under a 12-hour light/dark cycle at 25 ± 2 , and the relative humidity was 50 ± 5%. Male neonatal mice were selected at postnatal day (PND) 21. Since we aimed to mimic the prepubertal testicular injury induced byDEHPexposure, all male mice were randomly divided into four groups and treated by oral gavage from PND22 to PND35 with corn oil (Aladdin, C116023, China), or DEHP at a dose of 100 mg/kg/day (D100), 250 mg/kg/day (D250), or 500 mg/kg/day (D500).     Click to Show/Hide
Response Description	Di-(2-ethylhexyl) phthalate (DEHP) exposure led to testicular injury including excessive ROS accumulation. Prepubertal DEHP exposure induces ferroptosis in mouse testes. In particular, MEHP exposure leads to ferroptosis in Leydig and Sertoli cells via the HIF-1/HO-1 signaling pathway.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[8]
Regulator for Ferroptosis	Suppressor
Responsed Disease	Acute myocardial infarction [ICD-11: BA41]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hCMs (Human cardiomyocytes)
Response Description	Myocardial infarction is characterized by cardiomyocyte death and mitochondrial dysfunction induced by ischemia. FNDC5 overexpression and/or irisin administration elevated cell viability, decreased ferroptosis, and reversed mitochondrial impairments induced by hypoxia. Mechanistically, FNDC5/irisin reduced ferroptosis and reversed mitochondrial impairments by Nrf2/HO-1 axis in hypoxic cardiomyocytes.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[9]
Regulator for Ferroptosis	Driver
Responsed Disease	Pancreatic cancer [ICD-11: 2C10]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	PaTu 8988t cells	Pancreatic adenocarcinoma	Homo sapiens	CVCL_1847
	BxPC-3 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0186
	PANC-1 cells	Pancreatic ductal adenocarcinoma	Homo sapiens	CVCL_0480
	mEFs (Mouse embryonic fibroblasts)
	Panc02 cells	Pancreatic ductal adenocarcinoma	Mus musculus	CVCL_D627
In Vivo Model	All animal experiments were approved by the Ethics Committee of Jiangsu University. To investigate the role of the combination of erastin and vitamin C in inducing ferroptosis, Panc02 cells (1 x 105 cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts. When the tumors reached a volume of 50-100 mm3, the mice were randomly divided into four groups (five mice per group) and treated with DMSO (control), imidazole ketone erastin (IKE, MedChemExpress), vitamin C, or a combination of erastin and vitamin C. Mice were treated with 80 ul (400M) erastin by intratumoral injection and/or 4 g/kg vitamin C by intraperitoneal injection every 2 days.     Click to Show/Hide
Response Description	The combination of erastin and vitamin C mainly increases the levels of ferrous iron through the AMPK/NRF2/HMOX1 signaling pathway. Cotreatment with erastin and vitamin C also exhibited a synergistic effect in a pancreatic cancer xenograft model in mice.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[15]
Regulator for Ferroptosis	Driver
Responsed Disease	Health [ICD-11: N.A.]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
Response Description	Following addition of the JNK (MAPK8) inhibitor SP600125, the expression of HO-1 decreased, expression of FTH1 was increased and iron accumulation was decreased. Therefore, it was hypothesized that NPs induced ferroptosis in BV2 cells via the JNK/HO-1/FTH1 pathway.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[17]
Responsed Disease	Sepsis [ICD-11: 1G40]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
In Vivo Model	Briefly, female BALB/c mice (6-8 weeks, weighing 20-25 g, purchased from Hunan SJA Laboratory Animal Co., Ltd., Changsha, Hunan, China) were raised in specific pathogen-free conditions under controlled temperature (23-25 ) and humidity (40-80%) as well as a 12 h dark/light cycle for 1 week of acclimation. They were fed a standard chow diet and waterad libitum. Mice were anaesthetised with 2% isoflurane inhalation and underwent moderate caecal ligation and puncture in accordance with a previously reported protocol (Rittirsch etal.2009). Meanwhile, mice in the control groups were subjected to a sham operation. Buprenorphin (0.05 mg/kg) was injected for postoperative analgesia, and all mice were placed in cages immediately after the surgical procedures with free access to water and food (Rittirsch etal. 2009).     Click to Show/Hide
Response Description	Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[18]
Responsed Disease	Sepsis [ICD-11: 1G40]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	mVTs (Mouse ventricular tissues)
In Vivo Model	A total of 32 male C57BL/6 mice (25 g, 8 weeks old) were obtained from the Guangdong Medical Lab Animal Center and housed in the Laboratory Animal Service Center (Jinan University, Guangdong, China). Mice were anesthetized with isoflurane (RWD Life Science) inhalation at the concentration of 2.5% for anesthetic induction and then at 1% for anesthetic maintenance until the end of the CLP. During the experiment, the body temperature was kept at 36-38 with a heating pad. Anesthetized mice were subjected to midline laparotomy. The cecum was carefully separated to avoid blood vessels damage and the cecum was identified and punctured twice with a 22-gauge needle. Then, the abdominal cavity was closed with two epithelium layers, followed by a normal saline injection subcutaneously for resuscitation before mice were returned to the cage.     Click to Show/Hide
Response Description	The attenuation of sepsisinduced HO1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dexmedetomidine alleviates sepsis induced myocardial cellular injury.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[19]
Responsed Disease	Glioblastoma [ICD-11: 2A00]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
In Vivo Model	All BALB/C nude mice were purchased from Huafukang Biotechnology (Beijing, China). These mice were 5 weeks old and weighed 14-16 g. We established subcutaneous tumour-forming mouse model by injecting 5 x 106 U87 cells into the lateral abdomen of BALB/C nude mice. Animals were then treated with DHA solvent (50 mg/kg) by intragastric administration once a day for 26 days.     Click to Show/Hide
Response Description	Dihydroartemisinin could promote ferroptosis in glioma cells. Low expression of GPX4 and high expression of HMOX1 were identified in DHA treated glioma cells. MAZ was further identified as the direct target of long noncoding RNA (lncRNA) TUG1 through luciferase assay. Downregulated expression of TUG1 and upregulated expression of MAZ were identified in DHA treated glioma cells. TUG1 overexpression or inhibition of FTH1 expression could enhance the antiglioma effect of DHA in vitro and in vivo, providing a promising strategy to enhance the antitumor effect of DHA in glioma.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[20]
Responsed Disease	Glioblastoma [ICD-11: 2A00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Description	Lapatinib and siramesine was the most effective tyrosine kinase inhibitor and lysosome disruptor drug combination in inducing synergistic cell death in A549 and U87 cells. This cell death was through ferroptosis mediated by ROS and reduced expression of HO-1 in glioma cells.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[20]
Responsed Disease	Glioblastoma [ICD-11: 2A00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	U87 MG-Red-Fluc cells	Glioblastoma	Homo sapiens	CVCL_5J12
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
Response Description	Lapatinib and siramesine was the most effective tyrosine kinase inhibitor and lysosome disruptor drug combination in inducing synergistic cell death in A549 and U87 cells. This cell death was through ferroptosis mediated by ROS and reduced expression of HO-1 in glioma cells.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[21]
Responsed Disease	Central nervous system cancer [ICD-11: 2A02]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
Response Description	Subsequent studies have revealed that Polygonatum cyrtonemaHua Polysaccharides (PCP) alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. PCP has the development potential as a new drug candidate for treating CNS diseases.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[22]
Responsed Disease	Acute myeloid leukaemia [ICD-11: 2A60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	THP-1 cells	Childhood acute monocytic leukemia	Homo sapiens	CVCL_0006
	U-937 cells	Adult acute monocytic leukemia	Homo sapiens	CVCL_0007
	SKM-1 cells	Acute myeloid leukemia	Homo sapiens	CVCL_0098
Response Description	Honokiol decreased the viability of the targeted Acute myeloid leukemia cells, induced their cell cycle arrest at G0/G1 phase, and inhibited their colony-formation capacity. Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly. And HMOX1 was a critical target in honokiol-induced ferroptosis.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[23]
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
	SAOS-2 cells	Osteosarcoma	Homo sapiens	CVCL_0548
Response Description	3,5-bis((E)-2-fluorobenzylidene)piperidin-4-one hydrochloride (EF24) upregulated HMOX1 to suppress GPX4 expression to induce ferroptosis by increasing MDA level, ROS level and intracellular ferric ion level. Thus, EF24 might serve as a potential agent for the treatment of HMOX1-positive osteosarcoma patients.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[24]
Responsed Disease	Osteosarcoma [ICD-11: 2B51]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HEK-293T cells	Normal	Homo sapiens	CVCL_0063
	MG-63 cells	Osteosarcoma	Homo sapiens	CVCL_0426
	U2OS cells	Osteosarcoma	Homo sapiens	CVCL_0042
	MNNG/HOS Cl #5 cells	Osteosarcoma	Homo sapiens	CVCL_0439
Response Description	Zoledronic acid treatment decreased cell viability and promoted the increase in lipid peroxide content and PTGS2 expression. Our results indicate that zoledronic acid induces ferroptosis by decreasing ubiquinone content and promoting HMOX1 expression in osteosarcoma cells.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[25]
Responsed Disease	Nasopharyngeal cancer [ICD-11: 2B6B]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	MAPK signaling pathway			hsa04010
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	XWLC-05 cells	Lung adenocarcinoma	Homo sapiens	CVCL_IQ71
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SGC-7901 cells	Gastric carcinoma	Homo sapiens	CVCL_0520
	CNE2 cells	Normal	Homo sapiens	CVCL_6889
	U-251MG cells	Astrocytoma	Homo sapiens	CVCL_0021
	MCF-7 cells	Breast carcinoma	Homo sapiens	CVCL_0031
	K-562 cells	Chronic myelogenous leukemia	Homo sapiens	CVCL_0004
	ECV-304 cells	Bladder carcinoma	Homo sapiens	CVCL_2029
In Vivo Model	6-8 week old male balb/cnude micewere purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Nasopharyngeal carcinoma CNE2 cells were collected during logarithmic growth and rinsed with PBS twice and resuspended to a density of 1 x 107 cells/ml using fresh and cooled DMEM/F12 medium (free of FBS and antibiotics). Each mouse was inoculated subcutaneously with a 0.1 ml cell suspension on the right-side flank. Tumor-bearing mice were used for in vivo anticancer studies 8 days after inoculation when the average tumor volume reached ~200 mm3.     Click to Show/Hide
Response Description	Cephalosporin antibiotics showed highly specific and selective anticancer activity on nasopharyngeal carcinoma CNE2 cells both in vitro and vivo with minimal toxicity. Pathway analyses indicate apoptotic and the ErbB-MAPK-p53 signaling pathways are significantly enriched. HMOX1 represents the top one ranked upregulated gene by COS and overlaps with 16 of 42 enriched apoptotic signaling pathways. Inhibition of HMOX1 significantly reduced the anticancer efficacy of cefotaxime in CNE2 cells.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[26]
Responsed Disease	Oral squamous cell carcinoma [ICD-11: 2B6E]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Response Description	The current findings highlight that carnosic acid may re-sensitize cisplatin-resistant cells to cisplatin by inducing ferroptosis, which involves the inactivation of Nrf2/HO-1/xCT pathway. Hence, this research may support a promising therapeutic approach to overcome chemoresistance in Oral squamous cell carcinoma.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[27]
Responsed Disease	Oesophageal cancer [ICD-11: 2B70]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	KYSE30 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1351
	KYSE-510 cells	Esophageal squamous cell carcinoma	Homo sapiens	CVCL_1354
	MKN45 cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0434
In Vivo Model	KYSE30 cells were subcutaneously inoculated with 5 x 106 cells per site into both flanks on day 0. At 1 week after transplantation, tumor-bearing mice were randomly assigned to one of the following three groups: (1) saline as a control, (2) 10 mg/kg/day of 5-ALA, or (3) 30 mg/kg/day of 5-ALA. The treatment groups were orally administered 5-ALA once daily for 4 weeks, and the control group was orally administered saline during the same period.     Click to Show/Hide
Response Description	Modulation of GPX4 and HMOX1 by 5-aminolevulinic acid (5-ALA) induced ferroptosis in esophageal squamous cell carcinoma (ESCC). Furthermore, 5-ALA led to an increase in lipid peroxidation and exerted an antitumor effect in various cancer cell lines, which was inhibited by ferrostatin-1. Thus, 5-ALA could be a promising new therapeutic agent for ESCC.

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[28]
Responsed Disease	Gastric cancer [ICD-11: 2B72]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	MKN74 cells	Gastric tubular adenocarcinoma	Homo sapiens	CVCL_2791
	NUGC-4 cells	Gastric signet ring cell adenocarcinoma	Homo sapiens	CVCL_3082
Response Description	Andrographis exerted antitumor effects in gastric cancer cell lines (MKN74 and NUGC4) by inhibiting proliferation, reducing colony formation and enhancing apoptotic activity. Moreover, andrographis treatment altered the expression of ferroptosis-associated genes, including HMOX1, GCLC, and GCLM.
Experiment 2 Reporting the Ferroptosis-centered Drug Response of This Regulator				[32]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Wnt signaling pathway			hsa04310
	Ferroptosis			hsa04216
	Apoptosis			hsa04210
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
In Vivo Model	Seven-week-old male athymic nude mice (Envigo, Houston, TX) were housed under controlled conditions of light and fed ad libitum. Approximately 5 x 106 parental and 5FUR HCT116 cells were suspended in the matrigel matrix (BD Biosciences, Franklin Lakes, NJ) and subcutaneously injected into mice using a 27-gauge needle (n = 10 per group). Mice were randomly assigned to different treatment groups and 5FU (30 mg/kg body weight) or andrographis (125 mg/kg body weight) or their combination were given intraperitoneally on alternative days for up to 15 days.     Click to Show/Hide
Response Description	Combined treatment with andrographis was significantly more effective than 5FU and andrographis alone and that these effects were in part orchestrated through dysregulated expression of key genes (including HMOX1, GCLC, GCLM and TCF7L2) within the ferroptosis and Wnt-signaling pathways. Andrographis might offer a safe and inexpensive adjunctive therapeutic option in the management of colorectal cancer patients.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[29]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	HT29 cells	Colon cancer	Mus musculus	CVCL_A8EZ
	CT26 cells	Colon adenocarcinoma	Mus musculus	CVCL_7254
In Vivo Model	CT26 (1 x 105 cells/100 uL) were injected into thetail veinof male BALB/c mice. Then the mice were randomly divided into saline, vehicle, propofol, and sevoflurane groups (n = 5 per group). Saline, fat emulsion (as vehicle control of propofol), and propofol (200 mg/kg) were intraperitoneally injected, while sevoflurane (1.8-2.0%) was administered by inhalation for 2 h. In another set of experiments, coloncancer cells (CT26 and HT29) were pretreated with two doses of propofol (5 ug/mL, 10 ug/mL) or fat emulsion (as vehicle control of propofol) in a cell culture medium for 2 h. After washing with phosphate-buffered saline (PBS), the cells were harvested,counted on a hemacytometer and prepared. Cells (CT26: 1 x 105 cells/100 uL, HT29: 1 x 106 cells/100 uL) were finnally injected into mice through the tail vein.Lung metastasiswas detected via hematoxylin and eosin staining (HE) or ex vivo bioluminescence imaging.     Click to Show/Hide
Response Description	Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting colorectal cancer cell metastasis through Nrf2-mediated ferroptosis inhibition.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[30]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	SW480 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0546
	SW620 cells	Colon adenocarcinoma	Homo sapiens	CVCL_0547
In Vivo Model	5 x 106 HCT116 cells were inoculated subcutaneously in the underarm of Balb/c nude female mice (5-week old). The inoculated mice were randomly divided into two groups (6 mice each group). When the tumor reached 300 mm3, the drug group was given TalaA intraperitoneally at a dose of 6.0 mg/kg, and the control group was given the same dose of cosolvent-corn oil. The drug (or cosolvent) was injected every 2 days. Body weight and tumor volume were measured every 2 days.     Click to Show/Hide
Response Description	Talaroconvolutin A (TalaA) downregulated the expression of the channel protein solute carrier family 7 member 11 (SLC7A11) but upregulated arachidonate lipoxygenase 3 (ALOXE3), promoting ferroptosis. TalaA causes upregulation of HMOX1 which lead to the degradation of heme and the release of free iron, accumulating in mitochondria and giving rise to lipid peroxidation. TalaA could be a new potential powerful drug candidate for colorectal cancer therapy.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[31]
Responsed Disease	Colorectal cancer [ICD-11: 2B91]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
Response Description	Tagitinin C induces ferroptosis in colorectal cancer cells and has synergistic effect together with erastin. Mechanistically, tagitinin C induces ferroptosis through ER stress-mediated activation of PERK-Nrf2-HO-1 signaling pathway.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[33]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	Huh-7 cells	Hepatocellular carcinoma	Homo sapiens	CVCL_0336
Response Description	The study demonstrated that haloperidol strengthened sorafenib-induced ferroptosis in Hepatocellular carcinoma cell lines for the first time. During ferroptosis, haloperidol substantially increased the cellular levels of Fe2+, GSH and lipid peroxidation. Additionally, haloperidol induced the expression of HO-1.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[34]
Responsed Disease	Hepatocellular carcinoma [ICD-11: 2C12]			Disease Info
Pathway Response	MAPK signaling pathway			hsa04010
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell migration
	Cell proliferation
In Vitro Model	SMMC-7721 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_0534
	HCCLM3 cells	Adult hepatocellular carcinoma	Homo sapiens	CVCL_6832
In Vivo Model	Four-week-old nude mice (BALB/c) were used, and they were housed for 1 week in a specific pathogen-free (SPF) environment before experimentation. Each mouse received subcutaneous injections of 1 x 106 SMMC-7721 or HCCLM3 cells in 200 uL phosphate-buffered saline (PBS) into both flanks. One group was intraperitoneally injected every two days with EB at 25 or 50 mg/mouse body weight, for a total of 3 weeks. As a control, DMSO was used in another group. Tumor size was measured to calculate tumor volume, and mouse body weights were monitored every two days.     Click to Show/Hide
Response Description	Eupalinolide B (EB) exerts anti-proliferative activity in hepatic carcinoma by blocking cell cycle arrest at S phase and inducing ferroptosis mediated by endoplasmic reticulum (ER) stress, as well as HO-1 activation. And EB has the ability to inhibit cell proliferation and migration in hepatic carcinoma.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[35]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
	SPC-A1 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
In Vivo Model	Briefly, when tumours on transplanted nude mice reached around 100 mm3, the mice were randomized divided into eight groups: control, ginkgetin, DDP, ginkgetin + DDP, UAMC 3203, ginkgetin + UAMC 3203, DDP + UAMC 3203, ginkgetin + DDP + UAMC 3203. Both DDP (3 mg/kg) and ginkgetin (30 mg/kg) were administered by intraperitoneal injection, with 2 - 3 times per week and once per day, respectively. UAMC 3203 (10 mg/kg) was administered 5 days/week by intraperitoneally injection. Tumour size and body weight were measured 3 times per week. After dosing 31 days, the nude mice were sacrificed, and tumours were removed and weighed.     Click to Show/Hide
Response Description	The induction of ferroptosis mediated by ginkgetin was further confirmed by the decreased expression of SLC7A11 and GPX4, and a decreased GSH/GSSG ratio. Simultaneously, ginkgetin disrupted redox hemostasis in DDP-treated cells, as demonstrated by the enhanced ROS formation and inactivation of the Nrf2/HO-1 axis. Ginkgetin also enhanced DDP-induced mitochondrial membrane potential (MMP) loss and apoptosis in cultured non-small cell lung cancer (NSCLC) cells.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[36]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
In Vivo Model	Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5.     Click to Show/Hide
Response Description	The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[36]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell apoptosis
	Cell proliferation
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
In Vivo Model	Nude mice (5 weeks) were purchased from SLAC Int. (Shanghai, China). A549 cells (6 x 107 /ml) were collected and mixed with Matrigel (Corning, USA) at a 1:1 ratio by volume. Then, 100 ul cells were injected subcutaneously into the back region of nude mice to generate tumors with a size of 100 mm3 . Mice were randomly divided into four groups (n = 5/group): the control group, betulin group (10 mg/kg), gefitinib group (30 mg/kg), and the combined group. The control group was orally administered vehicle, while the betulin group, gefitinib group, and the combined group were orally administered betulin, gefitinib, and betulin plus gefitinib every other day. The tumor size and mice body weight were measured every other day too, and the volume was calculated according to the formula: tumor size (mm3 ) = (length x width2 ) x 0.5.     Click to Show/Hide
Response Description	The expression of SCL7A11, GPX4, and FTH1, which are negative regulators of ferroptosis, was significantly decreased under the combinative treatment of betulin and gefitinib. Moreover, the positive regulatory protein HO-1 was increased. These findings reiterated that the combination of betulin with gefitinib could trigger ferroptosis in KRASmutant non-small-cell lung cancer (NSCLC) cells.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[37]
Responsed Disease	Lung cancer [ICD-11: 2C25]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	NCI-H460 cells	Lung large cell carcinoma	Homo sapiens	CVCL_0459
In Vivo Model	When tumor volumes in xenograft nude mice reached an average of roughly 100 mm3, the mice were randomly divided into 3 groups of 6 mice each: control, ShtIX, and ShtIX + Fer-1. The treated group received ShtIX or ShtIX combined with Fer-1 injections into the tail vein of the mice every three days for 7 times, whereas the control group received saline. Every four days, the volume and weight of the tumors were measured. As soon as the test was completed, the nude mice were slaughtered, and the tumor tissues were retrieved. The in vivo experiments were approved by the Animal Care and Use Committee of Hainan Medical College and following the animal rules.     Click to Show/Hide
Response Description	S-3'-hydroxy-7', 2', 4'-trimethoxyisoxane (ShtIX) caused ferroptosis in Non-small cell lung cancer (NSCLC) cells, and inhibiting the Nrf2/HO-1 pathway can considerably exacerbate the effect of ShtIX-induced ferroptosis.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[38]
Responsed Disease	Breast cancer [ICD-11: 2C60]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	SK-BR-3 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0033
	MDA-MB-231 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0062
	MDA-MB-468 cells	Breast adenocarcinoma	Homo sapiens	CVCL_0419
	BT-549 cells	Invasive breast carcinoma	Homo sapiens	CVCL_1092
	MCF-10A cells	Normal	Homo sapiens	CVCL_0598
	786-O cells	Renal cell carcinoma	Homo sapiens	CVCL_1051
	A2780 cells	Ovarian endometrioid adenocarcinoma	Homo sapiens	CVCL_0134
	HCT 116 cells	Colon carcinoma	Homo sapiens	CVCL_0291
	Hep-G2 cells	Hepatoblastoma	Homo sapiens	CVCL_0027
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
	WPMY-1 cells	Normal	Homo sapiens	CVCL_3814
	U-87MG cells	Glioblastoma	Homo sapiens	CVCL_0022
	HT-1080 cells	Fibrosarcoma	Homo sapiens	CVCL_0317
In Vivo Model	MDA-MB-231 cells resuspended in PBS (2 x 106/100 m1) were injected subcutaneously into bothhind limbsof 4-6 weeks old femalenude mice. A week later, SGNI was administrated byintraperitoneal injectionat a dose of 112.5 mg/kg/3 d.     Click to Show/Hide
Response Description	Shuganning injection (SGNI) induced a ferroptotic cell death of Triple-negative breast cancer (TNBC) cells. Mechanistically, SGNI induced ferroptosis was dependent on HO-1, which promotes intracellular labile iron pool accumulation, and was alleviated by HO-1 knockdown and inhibition by tin protoporphyrin IX.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[39]
Responsed Disease	Ovarian cancer [ICD-11: 2C73]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	SK-OV-3 cells	Ovarian serous cystadenocarcinoma	Homo sapiens	CVCL_0532
	OVCAR-3 cells	Ovarian serous adenocarcinoma	Homo sapiens	CVCL_0465
In Vivo Model	Athymic nu/nu female mice aged 6-8 weeks (n = 9; mean weight, 20.21 ± 1.54 g) were purchased from the specific pathogen SPF (Beijing) Lab Animals Technology Co. Ltd. Mice were housed in a temperature- and humidity-controlled environment (20-24 , 45-55% humidity), with free access to food and water and in groups of three. All procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC ID: 17-3256) at Nantong University and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals.     Click to Show/Hide
Response Description	Nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following norcantharidin (NCTD) treatment. Collectively, NCTD may represent a potent anticancer agent in ovarian cancer cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/ HO-1/GPX4/xCT axis.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[40]
Responsed Disease	Corpus uteri cancer [ICD-11: 2C76]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell migration
In Vitro Model	Ishikawa cells	Endometrial adenocarcinoma	Homo sapiens	CVCL_2529
Response Description	Juglone as a natural quinone from C. cathayensisgreen peel could exert its anti-cancer activity by inducing iron dependent autophagy and inhibiting the migration of endometrial cancer (EC) cells. Subsequently, Fe2+ accumulation, lipid peroxidation, GSH depletion, the upregulation of HMOX1, and heme degradation to Fe2+ were reported. Juglone was involved in inducing autophagy and inhibiting cell migration and endoplasmic reticulum stress.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[41]
Responsed Disease	Prostate cancer [ICD-11: 2C82]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Glutathione metabolism			hsa00480
Cell Process	Cell ferroptosis
In Vitro Model	VCaP cells	Prostate carcinoma	Homo sapiens	CVCL_2235
	LNCaP cells	Prostate carcinoma	Homo sapiens	CVCL_0395
	LNCaP C4-2 cells	Prostate carcinoma	Homo sapiens	CVCL_4782
	22Rv1 cells	Prostate carcinoma	Homo sapiens	CVCL_1045
	RWPE-1 cells	Normal	Homo sapiens	CVCL_3791
	MDA-kb2 cells	Breast adenocarcinoma	Homo sapiens	CVCL_6421
Response Description	ITC-ARi 13 and buthionine sulfoximine (BSO) cooperatively downregulate AR and induce ferroptosis likely through increasing the accessibility of 13/12b to cellular targets, escalating free intracellular ferrous iron and attenuating GSH-centered cellular defense and adaptation. Further studies on the combination of ITC-ARi and GSH synthesis inhibitor could result in a new modality against castration-resistant prostate cancer (CRPC). Collectively, the combination of ITC-ARi 13 and BSO reveals a pro-ferroptotic role of Nrf2 through upregulating HO-1 under GSH-deficient conditions.

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[42]
Responsed Disease	Thyroid cancer [ICD-11: 2D10]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	Nthy-ori3-1 cells	Normal	Homo sapiens	CVCL_2659
	Nthy-ori3-1 cells	Normal	Homo sapiens	CVCL_2659
	FTC 238 cells	Thyroid gland follicular carcinoma	Homo sapiens	CVCL_2447
Response Description	Knockdown of HO-1 inhibits ferroptosis by upregulating the GPX4 expression in follicular thyroid cancer cells. We conclude that curcumin inhibits the tumorigenesis of follicular thyroid cancer via HO-1-induced activation of the ferroptosis signalling pathway.
Experiment 2 Reporting the Ferroptosis-centered Drug Response of This Regulator				[52]
Responsed Disease	Cardiomyopathy [ICD-11: BC43]			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	Two-month-old male New Zealand rabbits purchased from the Medical Experimental Animal Center of Bengbu Medical College were used as experimental subjects. Streptozotocin was dissolved in sterile saline and intraperitoneally injected into the rabbits at a dose of 80 mg/kg. The rabbits were allowed to eat freely after receiving the injection. The fasting blood glucose levels of the rabbits were monitored regularly. The diabetic rabbit model was considered successfully established when the fasting blood glucose level was measured as 11 mmol/L twice or 14 mmol/L once. Following successful modelling, grouping was performed as follows: blank control group (Con-Group), diabetic rabbit group (DM-Group), diabetic rabbit + every other day curcumin administration group (Qod-Group), and diabetic rabbit + daily administration group (Qd-Group).     Click to Show/Hide
Response Description	Curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[43]
Responsed Disease	Testicular dysfunction [ICD-11: 5A81]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	TM3 cells	Normal	Mus musculus	CVCL_4326
In Vivo Model	Eight-week-old adult male C57BL/6J mice were raised for 7 days before the study in a temperature and humidity controlled animal facility (22-25 , 50% relative humidity) with a12-h light/dark cycles. A total of 10 mice were randomly assigned into two groups. As described in our previous study, the control group was treated with 0.9% NaCl (0 mg CdCl2), and the treatment group was intraperitoneally injected with CdCl2 at a dose of 1.0 mg per kg of body weight for 1 week.     Click to Show/Hide
Response Description	Cadmium induced ferroptosis by iron homeostasis dysregulation, mediated by excessive activation of HMOX-1. The disruption of autophagy flow contributed to Cd-induced testicular dysfunction and attenuated testosterone synthesis.

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[44]
Responsed Disease	Parkinson disease [ICD-11: 8A00]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	C6 cells	Malignant glioma	Rattus norvegicus	CVCL_0194
Response Description	Gastrodin induced GPX4, Nrf2 and HO-1 expression to protect C6 cells from H2O2-induced ferroptosis. Gastrodin pretreatment effectively reduced H2O2-induced oxidative damage, indicating gastrodin is a potential antioxidant that reduced cytotoxic ROS. The role of gastrodin in ferroptosis presents a new perspective for understanding parkinson's disease.
Experiment 2 Reporting the Ferroptosis-centered Drug Response of This Regulator				[50]
Responsed Disease	Nervous system disease [ICD-11: 8E7Z]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	HT22 cells	Normal	Mus musculus	CVCL_0321
Response Description	Gastrodin (GAS) is a component of Gastrodia elata Blume, with strong antioxidant activity in neurodegenerative diseases. GAS increased the nuclear translocation of Nrf2, up-regulated the downstream HO-1 protein expression in HT-22 cells following treatment with glutamate.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[45]
Responsed Disease	Alzheimer disease [ICD-11: 8A20]			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	B6.1291-Nfe2l2tm1Ywk/J (Nrf2-/-mice, 017009)and wild-type C57BL/6 were originally from the Jackson Laboratory. Grouping and administration were started when weighing approximately 28-33 g. All mice were housed in a laboratory environment with free access to adequate food and water under a 12 h/12 h light/dark cycle at 22 ± 1 and 55 ± 5% humidity. All procedures conformed to the protocols of the Animal Welfare Commission and Ethical Committee of Southern Medical University. The Nrf2-/- mice were identified by genotyping as shown in Fig.1B. WT and Nrf2-/- mice were randomly assigned to 32 groups (3 groups for WT mice and 3 groups for Nrf2-/- mice) as follows: a sham group, sham + Ab1-42 group, and Salidroside + Ab1-42 group.     Click to Show/Hide
Response Description	Salidroside plays a neuroprotective role by inhibiting neuronal ferroptosis in A1-42-induced Alzheimer's disease mice and Glu-injured HT22 cells, and its mechanism is related to activation of the Nrf2/HO1 signaling pathway.

In total 2 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[46]
Responsed Disease	Subarachnoid Hemorrhage [ICD-11: 8B01]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	SAH model was constructed by applying endovascular perforation in the rats, according to the protocol introduced in a previous study (Wei et al., 2020), except for slight modifications. Briefly, after performing intraperitoneal anesthesia with 40 mg/kg sodium pentobarbital, the right common carotid, external and internal carotid arteries of the rats were exposed and isolated. The right external carotid artery was ligated, and a 4-0 single-strand nylon thread was used to insert the right internal carotid artery through the stump of the external carotid artery and the bifurcation of the common carotid artery. When resistance is felt when the suture enters the intracranial segment, proceed approximately 3 mm to penetrate internal carotid artery at the bifurcation of middle cerebral artery. The suture was held in this position for 10 s and was then withdrawn. The rats in the Sham group went through an identical procedure, without the suture at the point of resistance. Throughout the experiment, the body temperature of the rats was sustained at around 37 by using a thermal blanket. After the wounds were sutured, the rats were placed in a separate cage and neurological function was closely observed.     Click to Show/Hide
Response Description	Astragaloside IV (AS-IV) triggered Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of subarachnoid hemorrhage (SAH). The Nrf2 inhibitor ML385 blocked the beneficial effects of neuroprotection. These results consistently suggest that ferroptosis is profoundly implicated in facilitating EBI in SAH, and that AS-IV thwarts the process of ferroptosis in SAH by activating Nrf2/HO-1 pathway.
Experiment 2 Reporting the Ferroptosis-centered Drug Response of This Regulator				[48]
Responsed Disease	Cerebral ischaemic stroke [ICD-11: 8B11]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	hBCs (Brain cells)
In Vivo Model	1% sodium pentobarbital (40 mg/kg) was administered to the rats intraperitoneally to anesthetize them before placing them in a brain stereotaxic device. An incision was created in the midline of the neck to expose the common internal and external carotid arteries. After ligating and cutting the external carotid artery on the left side, a 3-mm stump was exposed. We then perforated the carotid artery at the bifurcation of the middle and anterior cerebral arteries utilizing an 18-20-mm-long surgical filament (0.26 mm diameter; Beijing Cinontech Co. Ltd., China) was threaded through the external carotid artery stump into the internal carotid artery and left in situ for 120 min. After that, the filament was withdrawn to facilitate reperfusion. Rats in the sham surgery group received the identical procedure as the other rats but without filament insertion.     Click to Show/Hide
Response Description	Astragaloside IV (AS-IV) administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-, interleukin-1 (IL-1), IL-6, and NF-B, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[47]
Responsed Disease	Cerebral ischemia [ICD-11: 8B10]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	rPAs (Rat primary astrocytes)
In Vivo Model	Rats were anesthetized withisoflurane(2-3% oxygen) and placed in asupine position. And theright common carotid artery (CCA),external carotid artery (ECA), andinternal carotid artery (ICA) were exposed in sequence and separated carefully. Then we ligated the CCA and the ECA in turn, and at the same time, we clamped the internal carotid artery with an arterial clamp. Finally, we inserted a silicone nylon monofilament from the CCA into themiddle cerebral arteryand temporarily fixed it. After 1.5 h ofischemia, the monofilament was taken out and the blood vessels were ligated at theincision. The neck wound was sutured with surgical sutures. Subsequent experiments were performed after 12 h ofreperfusion. In thesham operationrats, except for the absence of the monofilament, the sham operation rats underwent the same surgical procedures as the MCAO/R model rats.     Click to Show/Hide
Response Description	Our results indicated the critical role of ferroptosis in cerebral ischemia reperfusion injury. For the first time, we showed that the significant neuroprotective effects of b-Caryophyllene (BCP) in attenuating ischemic stroke injury are correlated with ferroptosis regulation, and its mechanism is associated with activation of the NRF2/HO-1 axis.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[49]
Responsed Disease	Thromboembolic stroke [ICD-11: 8B20]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BV-2 cells	Normal	Mus musculus	CVCL_0182
	Neuro-2a cells	Neuroblastoma	Mus musculus	CVCL_0470
	RAW 264.7 cells	Leukemia	Mus musculus	CVCL_0493
In Vivo Model	Brain penetration study was carried out by TCG Lifesciences Ltd (Kolkata, India) in male BALB/c mice (6-8 weeks old; 18-20 g, in-house breeding). Mice were housed individually under 12/12 h lightdark cycle with free access to food and water. In two experiments 10 mg/kg or 30 mg/kg of ADA-409-052 (HPLC Purity: 99.7%) dissolved in Tween-80 (0.5%, Merck, Germany) -methylcellulose (Sigma) solution was administered as a single bolus by oral gavage (p.o.). ADA-409-052- or vehicle-administered mice were sacrificed 0.75, 4, and 24 h later (n = 3/group).     Click to Show/Hide
Response Description	ADA-409-052 inhibits tert-Butyl hydroperoxide (TBHP)-induced lipid peroxidation (LP) and protects against ferroptotic cell death triggered by glutathione (GSH) depletion or glutathione peroxidase 4 (GPx4) inhibition in neuronal cell lines. Moreover, ADA-409-052 efficiently reduces infarct volume, edema and expression of pro-inflammatory genes in a mouse model of thromboembolic stroke. In addition, ADA-409-052 reduced the expression of stroke-induced Hmox1.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[51]
Responsed Disease	Age-related macular degeneration [ICD-11: 9B75]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	ARPE-19 cells	Normal	Homo sapiens	CVCL_0145
In Vivo Model	In this study, sixteen-week-old male C57BL/6 mice were used and housed in a standard laboratory environment. Forin vivostudies, left eyes were pretreated with a single intravitreal injection of DMSO (1 uL) or 1X PBS (1 uL), and right eyes were pretreated with Fer-1 (30 uM, a single intravitreal injection, 1 uL), DFO (100 uM, a single intravitreal injection, 1 uL), or ZnPP (50 mg/kg, intraperitoneal injection once a week). 15 min later, injection of NaIO3(35 mg/kg, a single injectionviatail vein), or 1X PBS (a single injectionviatail vein, 75 uL) has been performed. After 2 weeks, mice were used for subsequent experiments.     Click to Show/Hide
Response Description	Sodium iodate-induced oxidative stress model has been identified to be heme oxygenase-1 (HO-1)-regulated ferroptosis, which is controlled by the Nrf2-SLC7A11-HO-1 hierarchy. These findings highlight that targeting HO-1-mediated RPE ferroptosis could serve as an effectively retinal-protective strategy for retinal degenerative diseases prevention, including age-related macular degeneration (AMD).

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[53]
Responsed Disease	Ischemia/reperfusion injury [ICD-11: DB98]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	MLE-12 cells	Normal	Mus musculus	CVCL_3751
In Vivo Model	In vivo, the LIRI model was established as described earlier. All mice were anesthetized with pentobarbital administered intraperitoneally (50 mg/kg, Sigma-Aldrich, MO, USA). After endotracheal intubation, the mice were ventilated using a rodent ventilator (MiniVent, Harvard Apparatus, USA), with the title volume set to 7 ml/kg, the respiratory rate set to 120 times/min, and the inspiratory/expiratory ratio set to 1: 2. A noninvasive clamp was used to interrupt the left pulmonary hilum, causing lung ischemia. The clamp was released after 60 minutes of ischemia, and the left lung was reperfused for 120 minutes. Animals were euthanized via cervical dislocation at the end of the experiment. Following that, lung specimens and bronchoalveolar lavage fluid were harvested for analysis. All procedures except lung ischemia were performed on mice in the sham group.     Click to Show/Hide
Response Description	As a result, irisin postconditioning may protect against lung I/R damage by suppressing ferroptosis via the Nrf2/HO-1 signaling axis.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[54]
Responsed Disease	Ischemia/reperfusion injury [ICD-11: DB98]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	HUVECs (Human umbilical vein endothelial cells)
In Vivo Model	Mice were exposed to 12/12 h of light/darkness and given free access to food and water. All C57BL/6J mice were fasted for 12 h and anesthetized by intraperitoneal injection of 1% sodium pentobarbital before modeling. Later, the superior mesenteric artery (SMA) was subjected to 45 min of global no-flow ischemia, followed by 90 min of reperfusion to induce IIRI. The successful model could be revealed by the microcirculation detector. In order to investigate the effects of APG, mice were randomly divided into different groups: Sham group, IIRI group, APG groups (2 mg/kg, 4 mg/kg and 8 mg/kg), ZnPPIX group (Protoporphyrin Zinc(), Dalian Meilun Biotech Co., Ltd., China, 10mg/kg), Selegiline group (10 mg/kg, Shandong Topscience Biotech Co., Ltd., China) and the ZnPPIX + Selegiline group (10 mg/kg ZnPPIX and 10 mg/kg Selegiline). As mentioned above, drug was intraperitoneal injected after a 10-min-ischemia.     Click to Show/Hide
Response Description	MST analysis suggested that Apigenin could specifically bind to heme oxygenase 1 (HO-1) and monoamine oxidase b (MAO-B). Simultaneously, APG could attenuate ROS generation and Fe2+ accumulation, maintain mitochondria function thus inhibit ferroptosis and alleviate intestinal ischemia-reperfusion injury.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[55]
Responsed Disease	Ischemia/reperfusion injury [ICD-11: DB98]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	AML12 cells	Normal	Mus musculus	CVCL_0140
In Vivo Model	The mice were randomly divided into four groups of six: sham + vehicle, sham + DMF, IR + vehicle, and IR + DMF. The mice were supplemented with DMF at a concentration of 100 mg/kg or DMSO by daily oral gavage for a week before surgery, as previously reported. As stated in a prior study, the partial warm liver IRI model was developed. Briefly, the sham group only had free hepatic portal blood vessels after laparotomy, and the blood flow was not obstructed. As for the hepatic IR group, the blood supply to the left and mid-hepatic lobes was blocked, resulting in 70% mouse liver IRI for 90 min. The mice were put on a heated blanket after surgery in order to maintain body temperature and monitor vital signs. Blood supply was restored for 6 h. Died mice were eliminated for testing prior to sample collection. The mice were euthanized after the sample were obtained. The same experimenter carried out all surgeries.     Click to Show/Hide
Response Description	NRF2 knockdown notably decreased the expression of SLC7A11 and HO-1 and blocked the anti-ferroptosis effects of dimethyl fumarate (DMF). DMF inhibits ferroptosis by activating the NRF2/SLC7A11/HO-1 axis and exerts a protective effect against hepatic ischemia-reperfusion injury.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[56]
Responsed Disease	Acute pancreatitis [ICD-11: DC31]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	AR42J cells	Digestive system neoplasms	Rattus norvegicus	CVCL_0143
In Vivo Model	Male C57BL/6 mice (8 weeks old; SPF; weighing 24-26 g, n = 16 in total) were purchased from SPF (Beijing) Biotechnology Co., Ltd. All mice were housed in an environmentally controlled room at a temperature ranging from 20 to 24 on a 12 h light/dark cycle and used in the experiments following an overnight fast with water, availablead libitum. All procedures followed the Principles of Laboratory Animal Care (NIH publication number 85Y23, revised in 1996), and the experimental protocol was approved by the Animal Care Committee, Nanjing Medical University (NMU-2021JK-085).     Click to Show/Hide
Response Description	Taken together, the present study, to the best of our knowledge, is the first to reveal a protective role for Ginsenoside Rg3 in mice with acute pancreatitis by suppressing oxidative stressrelated ferroptosis and the activation of the NRF2/HO1 pathway.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[57]
Responsed Disease	Acute kidney failure [ICD-11: GB60]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
	Cell apoptosis
In Vitro Model	HK-2 cells	Normal	Homo sapiens	CVCL_0302
In Vivo Model	Six-week-old male Wistar rats (170-200 g) were obtained from Changsheng Biotechnology Co., Ltd. (Changchun, China), and all of them were fed under SPF-conditions. The rats were acclimatized to natural light/dark cycles at a controlled temperature of 22 + 2 with free access to food and water. The experiment was comprised of four groups: the C group (0.5% carboxymethyl cellulose sodium [CMC-Na], n = 6); the Dio group (dioscin-treated rats, n = 6); the CP group (cisplatin-treated mice, n = 6); and the Dio + CP group (dioscin plus cisplatin-treated rats, n = 6). Rats were gavaged with dioscin (60 mg/kg) for ten days, and cisplatin (10 mg/kg) was intraperitoneally injected once on the seventh day.     Click to Show/Hide
Response Description	Dioscin exerts a reno-protective effect by decreasing renal oxidative injury, apoptosis and ferroptosis through the Nrf2/HO-1 signaling pathway, providing a new insight into acute kidney injury prevention.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[58]
Responsed Disease	Lung injury [ICD-11: NB32]			Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	BEAS-2B cells	Normal	Homo sapiens	CVCL_0168
In Vivo Model	Male C57BL/6 mice (8 weeks, 23-25 g) were obtained from Beijing Hua Fu Kang Biotechnology Co. LTD (Beijing, China). A total of 96 mice were randomly divided into 6 groups (n = 16 per group): Sham group, LPS group, Fer-1 group, Fe group, Sev group, and Fe + Sev group. Mice were given 5 mg/kg LPS intranasally to construct LPS-induced ALI model. To study the role of ferroptosis in ALI, the mice in the Fer-1 or Fe groups were administered with Fer-1 (0.8 mg/kg; Ferrostatin-1, the inhibitor of ferroptosis) or Fe (8 mg/kg; Fe-citrate (III), ferroptosis inducer) via tail vein injection once a day for 3 consecutive days before treatment with LPS, respectively. To study the effect of Sev on ALI mice, the mice in Sev group were treated with LPS for 2 h, and then Sev, delivered by gaseous admixture (oxygen) at a concentration of 3% via a calibrated vaporizer, was administered via an endotracheal tube for 4 h. In order to study the effect of Sev on ferroptosis, the mice in Fe + Sev group were administered with Fe via tail vein injection once a day for 3 consecutive days, and then treated with LPS and Sev. Sham group was given 0.9% NaCl (containing 0.1% DMSO).     Click to Show/Hide
Response Description	Sevoflurane (Sev) could eliminate the worsening effects of ferroptosis inducer Fe-citrate on LPS-induced acute lung injury (ALI) to a certain extent. Sev inhibited ferroptosis by up-regulating HO-1 expression to reduce LPS-induced ALI, which may provide a possible mechanism for the application of Sev in clinical anesthesia.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[59]
Responsed Disease	Injury of intra-abdominal organs [ICD-11: NB91]			Disease Info
Pathway Response	NF-kappa B signaling pathway			hsa04064
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell autophagy
	Cell apoptosis
In Vitro Model	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In Vivo Model	Mice were randomly divided into four groups as follows (n = 5): (1) control, (2) APAP (MCE, Monmouth Junction, NJ, USA), (3) olive oil + APAP (oil + APAP), and (4) ASX (Energy Chemical, Shanghai, China) dissolved in olive oil + APAP (ASX + APAP). Astaxanthin was dissolved in olive oil to obtain a mixture of 20 mg/mL. Mice in groups 3 and 4 were given a dose of olive oil and a mixture of 5 mL/kgBW by gavage every day for 2 weeks. On day 15, mice in groups 2, 3, and 4 were given a peritoneal injection of 500 mg/kg APAP to induce liver injury. The mice were fasted for 12 h before the administration of APAP. Ten hours after APAP administration, blood and liver tissue were collected for further examination and analyses. Blood was centrifuged to obtain supernatants,which were stored at -80. Liver tissues were immediately removed from each animal, and homogenates were processed with formaldehyde and glutaraldehyde for protein and histological analysis.     Click to Show/Hide
Response Description	Astaxanthin reduced inflammation through the NF-B pathway, inhibited oxidative stress and ferroptosis, and increased autophagy through the Nrf2/HO-1 pathway, ameliorating acetaminophen-induced liver injury in vivo and in vitro.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[2]
Responsed Disease	Injury of intra-abdominal organs [ICD-11: NB91]			Disease Info
Pathway Response	Ferroptosis			hsa04216
	Fatty acid metabolism			hsa01212
Cell Process	Cell ferroptosis
In Vitro Model	L-02 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6926
In Vivo Model	Male C57BL/6 mice were from the Experimental Animal Center of Xian Jiaotong University. The animal experiment procedures were performed in accordance with the Guide of Laboratory Animal Care and Use from the United States National Institution of Health and were approved by the Laboratory Animal Care Committee (LACC) of Xian Jiaotong University, China (No. XJTULAC2017-207). Mice were initially housed for 7 days to adjust to the environment. The experimental design included five groups (n = 10 per group): the control group included the saline control (0.9% saline) group, and the test groups included APAP, APAP + UTI (5 x 104 units/kg and 1 x 105 units/kg), APAP + Fer-1 (10 mg/kg), and APAP + Res (50 mg/kg) treatments administered by tail vein or intraperitoneal injection.     Click to Show/Hide
Response Description	Ulinastatin plays a role in mitigation of APAP-induced acute liver injury by inhibiting ferroptosis-induced lipid peroxide accumulation, and the effect of UT1 was mediated by the NRF2/HO-1 pathway and SIRT1 expression.

In total 1 item(s) under this drug				Drug Info
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator				[60]
Responsed Disease	Injury of intra-abdominal organs [ICD-11: NB91]			Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	AML12 cells	Normal	Mus musculus	CVCL_0140
In Vivo Model	APAP-induced liver injury model was induced byintraperitoneal injection 300 mg/kg APAP. The mice of APAP + abietic acid (10, 20, 40 mg/kg) were given abietic acid by intraperitoneal injection 1 h before APAP treatment. The doses of abietic acid used in this study were based on previous studies. Twelve hours later, the mice were sacrificed after anesthesia with 1%pentobarbital (50 mg/kg) injected intraperitoneally and the samples were collected.     Click to Show/Hide
Response Description	APAP could increase malondialdehyde (MDA) and Fe2+ levels, and decrease ATP and glutathione (GSH) levels, as well as glutathione peroxidase 4 (GPX4) and xCT expression. However, these changes induced by APAP were prevented by abietic acid, indicating abietic acid could inhibit APAP-induced ferroptosis. Furthermore, abietic acid inhibited APAP-induced liver injury, NF-B activation and increased the expression of Nrf2 and HO-1.