TABLE 1.
List of clinical trials associated with ferroptosis‐targeted drugs.
| Agents | Mechanism and/or target | Effects | Experimental model | Outcomes | Indication | Trial phase and identifier number | References |
|---|---|---|---|---|---|---|---|
| Targeting lipid metabolism pathway | |||||||
| Rosiglitazone | ACSL4 inhibitor | Inhibiting ferroptosis | Renal Gpx4−/− mice; I/R injury mice 14 | Reduces mortality associated with acute kidney injury; prevents I/R intestinal injury | Solid tumor malignancies | Phase II NCT04114136 | 14 , 234 |
| Prostate cancer | Phase III NCT00182052 | ||||||
| Ulcerative colitis | Phase II NCT00065065 | ||||||
| HIV infection | Phase II NCT00367744 | ||||||
| Sarcoma | Phase II NCT00004180 | ||||||
| Alzheimer's disease | Phase I NCT00688207 | ||||||
| MASH | Phase II NCT00492700 | ||||||
| Kidney transplant | Phase II NCT00309309 | ||||||
| Baicalein | ALOX12/15 inhibitor; ACSL4 inhibitor | Inhibiting ferroptosis | Cisplatin and folic acid‐induced AKI in mice; CPT‐11‐induced delayed diarrhea in rat; heart I/R injury in rat | Alleviates renal inflammatory responses and AKI; alleviates colonic pathological injury and decreased inflammatory factor; improves myocardial I/R challenge‐induced ST segment elevation, coronary flow, left ventricular systolic pressure, infarct area, and pathological changes | Influenza | Phase II NCT03830684 | 271 , 272 , 273 |
| Zileuton | ALOX5 selective inhibitor | Inhibiting ferroptosis | HT22 cells | Protects HT22 neuronal cells from glutamate oxidative toxicity in a ferroptosis‐dependent mechanism. | Chronic myelogenous leukemia | Phase I NCT02047149; Phase I NCT01130688 | 274 |
| Sickle cell disease | Phase I NCT01136941 | ||||||
| Head and neck cancer; lung cancer | Phase II NCT00056004; Phase II NCT00070486 | ||||||
| Tobacco use disorder | Phase II NCT02348203; Phase II NCT01021215 | ||||||
| Acne vulgaris | Phase II NCT00098358 | ||||||
| NDGA | Pan‐LOX inhibitor | Inhibiting ferroptosis | Acute lymphoblastic leukemia cells | Blocks RSL3‐induced lipid peroxidation and cell death | Prostate cancer | Phase II NCT00678015 | 275 |
| High grade glioma | Phase I NCT02575794 | ||||||
| Brain and central nervous System tumors | Phase I NCT00404248 | ||||||
| Targeting iron homeostasis | |||||||
| DFO | Iron chelator | Inhibiting ferroptosis | MCD‐induced MASH in mice; hepatic I/R injury in mice; aged (15–18 months) C57 mice intraperitoneally injected with LPS; diabetic MCAO rat; MCAO rat | Attenuates the Severity of MASH; attenuates hepatic I/R injury and lipid peroxidation; improves inflammation and sickness behavior in aged mice treated with LPS; prevents vasoregression and microglia activation while improving AQP4 polarity as well as blood‐brain barrier permeability; reduce the area of cerebral infarction, improve the pathological structure of cerebral ischemia rats | Cardiomyopathy Hypotension, acute renal failure Ischemic stroke AKI Aneurysmal subarachnoid hemorrhage | Phase IV NCT00800761 | 236 , 266 , 276 , 278 |
| Phase II NCT0087088 | |||||||
| Phase II NCT00777140 | |||||||
| Phase II NCT04633889 | |||||||
| Phase II NCT04566991 | |||||||
| DFP | Iron chelator | Inhibiting ferroptosis | DSS‐induced ulcerative colitis in mice | Relieves the inflammation and impaired colon, and increase body weight | Acute myocardial infarction type 1 | Phase I NCT05604131 | 279 |
| Neurodegeneration | Phase II NCT00907283 | ||||||
| Stroke | Phase II NCT05111821 | ||||||
| DFX | Iron chelator | Inhibiting ferroptosis | Myocardial I/R injury in mice | Reduces myocardial injury and infarct size | Myelodysplasia | Phase II NCT03387475 | 280 |
| Sickle cell disease | Phase II NCT05392101 | ||||||
| DXZ | Iron chelator | Inhibiting ferroptosis | DOX‐ and I/R‐induced cardiomyopathy in mice | Prevents DOX‐induced cardiomyopathy and reduces the severity of cardiac I/R Injury. | During congenital heart surgery | Phase II NCT04997291 | 230 |
| Acute myeloid leukemia | Phase II NCT03589729 | ||||||
| Targeting redox systems | |||||||
| SAS | SLC7A11 inhibitor | Promoting ferroptosis | H22‐luc hepatoma ascites mice | Reduces tumor burden | Glioma; glioblastoma; recurrent glioblastoma | Phase I NCT04205357 | 281 |
| Breast cancer; chronic pain due to malignancy | Phase II NCT03847311 | ||||||
| Sorafenib | SLC7A11 inhibitor | Promoting ferroptosis | MGC803 xenografts; HT‐1080 xenografts; 786‐O xenografts | Suppresses tumor growth | Hepatocellular carcinoma | Phase IV NCT01203787 | 282 , 283 , 284 |
| Acute myeloid leukemia | Phase III NCT01371981 | ||||||
| Neuroblastoma | Phase II NCT02559778 | ||||||
| Carcinoma, non‐small‐cell lung | Phase III NCT00449033 | ||||||
| BSO | Inhibition of GCL; GSH‐depleting | Promoting ferroptosis | BJ‐derived cell; HT‐1080 cells; | Induces selective lethality in BJ‐derived tumorigenic cells expressing oncogenic HRAS; inhibits HT‐1080 cells viability | Neuroblastoma | Phase I NCT00005835, Phase I NCT00002730 | 40 , 172 |
| Cisplatin | GSH‐depleting | Promoting ferroptosis | MKN‐45 xenografts; LLC xenografts | Suppresses tumor growth | NSCLC | Phase III NCT01656551 | 285 , 286 |
| Bladder cancer | Phase III NCT04574960 | ||||||
| Cervical cancer | Phase III NCT01561586 | ||||||
| Cancer of pancreas | Phase II NCT03649321 | ||||||
| NAC | GSH synthesis regulator | Inhibiting ferroptosis | ICH in mice; polycystic ovary syndrome model in rats; diabetic nephropathy model in beagle; intermittent hypoxia‐induced myocardial injury in mice | Improves functional recovery at least 7 days following ICH in mice; attenuates gravid uterine and placental ferroptosis in a PCOS‐like rat model with fetal loss; ameliorates kidney injury in diabetic nephropathy; alleviates intermittent hypoxia‐related myocardial injury | Progressive MS | Phase II NCT05122559 | 287 , 288 , 289 , 290 |
| Neurofibromatosis 1 | Phase II NCT04481048 | ||||||
| Skin disorder | Early phase 1 NCT05287724 | ||||||
| Mitochondrial disease | Phase I NCT05241262 | ||||||
| Diabetic neuropathies | Phase IV NCT04766450 | ||||||
| Vascular cognitive impairment no dementia | Phase II NCT03306979 | ||||||
| SLE | Phase II NCT00775476 | ||||||
| Mifepristone | Promoting GSH synthesis | Inhibiting ferroptosis | Acetaminophen induced liver injury in mice | Protects against APAP‐induced acute liver injury, evidenced by decreased ALT, AST level and histological recovery | Meningioma | Phase III NCT03015701 | 291 |
| Breast cancer | Phase III NCT05016349 | ||||||
| NSCLC | Phase II NCT02642939 | ||||||
| Prostate cancer | Phase II NCT00140478 | ||||||
| Hepatitis C virus infection | Phase II NCT00255177 | ||||||
| Endocrine disease; diabetes | Phase II NCT01419535 | ||||||
| WA | Alkylation of GPX4 | Promoting ferroptosis | IMR‐32 xenografts | Suppresses the growth and relapse rate of neuroblastoma xenografts | Recurrent ovarian cancer | Phase I NCT05610735 | 292 |
| Gemcitabine | Inhibiting GPX4 | Promoting ferroptosis | A549 cells | Inhibits A549 cells proliferation | Pancreatic cancer | Phase II NCT06015659 | 293 |
| Biliary tract cancer | Phase II NCT05357196 | ||||||
| Adult solid tumor | Phase I NCT05147272 | ||||||
| SeMet | GPX4 activators | Inhibiting ferroptosis | DOX‐induced acute cardiotoxicity in mice | Protects mice from DOX‐induced cardiotoxicity | Liver disease | Phase IV NCT01650181 | 294 |
| Precancerous/nonmalignant condition; prostate cancer | Phase III NCT00030901 | ||||||
| Lung cancer | Phase II NCT00526890 | ||||||
| Colorectal cancer | Phase II NCT00625183 | ||||||
| ccRCC | Phase I NCT05363631 | ||||||
| Brequinar | DHODH inhibitor | Promoting ferroptosis | NCI‐H226 xenografts and TC494 lung cancer PDXs | Suppresses the tumor growth of GPX4low xenografts | SARS‐CoV‐2 infection | Phase II NCT04575038 | 50 |
| Acute myeloid leukemia | Phase II NCT03760666 | ||||||
| Leflunomide | DHODH inhibitor | Promoting ferroptosis | SB‐driven hepatocarcinogenesis in mice | Constrains tumor mass and number, and achieves a much healthier liver and prolonged survival time | SARS‐CoV‐2 infection | Phase III NCT05007678 | 189 |
| Neuroendocrine tumors | Phase II NCT06540937 | ||||||
| Brain and central nervous system tumors | Phase II NCT00003775 | ||||||
| Idiopathic pulmonary Hemosiderosis | Phase II NCT05937191 | ||||||
| Advanced pancreatic adenocarcinoma | Phase I NCT06454383 | ||||||
| Menaquinone‐4 | RTA | Inhibiting ferroptosis | Hepatocyte‐specific Gpx4−/− mice; I/R injury in mice | Protects against related pathologic changes in liver; Protects against liver or kidney I/R injury in mice | Diabetes | Phase IV NCT00960973 | 62 |
| Osteoporosis | Phase IV NCT00548509 | ||||||
| Hepatocellular carcinoma | Phase III NCT00165633 | ||||||
| Promethazine | RTA | Inhibiting ferroptosis | Cisplatin‐induced AKI and LPS/galactosamine‐induced liver injury in mice | Ameliorates AKI and increases the survival rate in mice; improves LPS/GalN‐induced acute liver injury | Pruritus | Phase IV NCT04805073 | 295 |
| Diabetic gastroparesis | Phase II NCT02130622 | ||||||
| Edaravone | RTA | Inhibiting ferroptosis | CSDS depression model in mice; permanent MCAO mice | Ameliorates depressive and anxiety‐like behaviors; alleviates cerebral ischemic injury in the mice with permanent MCAO | Acute ischemic stroke | Phase III NCT02430350 | 296 , 297 |
| Nasopharyngeal carcinoma, brain necrosis | Phase II NCT01865201 | ||||||
| Myocardial infarction | Phase IV NCT00265239 | ||||||
| Cerebral infarction | Phase IV NCT00200356 | ||||||
| ALS | Phase III NCT00415519 | ||||||
| CuATSM | RTA | Inhibiting ferroptosis | Mouse embryonic fibroblasts and hippocampal cells | Rescues embryonic fibroblasts and hippocampal cells from ferroptosis | ALS | Phase III NCT04082832 | 298 |
Abbreviations: ACSL4, acyl‐CoA synthetase long‐chain family member 4; AKI, acute kidney injury; ALOX12/15, arachidonate lipoxygenases 12/15; ALS, amyotrophic lateral sclerosis; ALT, alanine aminotransferase; APAP, acetaminophen; AST, aspartate aminotransferase; BSO, buthionine sulfoximine; ccRCC, clear cell renal cell carcinoma; CSDS, chronic social defeat stress; DFO, deferoxamine; DFP, deferiprone; DFX, deferasirox; DHODH, dihydroorotate dehydrogenase; DOX, doxorubicin; DSS, dextran sulfate sodium; DXZ, dexrazoxane; GCL, glutamate–cysteine ligase; Gpx4, glutathione peroxidase 4; GSH, glutathione; I/R, ischemia/reperfusion; ICH, intracranial hemorrhage; LLC, Lewis lung carcinoma; LPS, lipopolysaccharide; MASH, metabolic dysfunction‐associated steatohepatitis; MCAO, middle cerebral artery occlusion; MCD, methionine/choline‐deficient diet; MS, multiple sclerosis; NAC, N‐acetylcysteine; NCT, national clinical trial; NDGA, nordihydroguaiaretic acid; NSCLC, non‐small cell lung cancer; PCOS, polycystic ovary syndrome; PDXs, patient‐derived xenografts; RTA, radical‐trapping antioxidant; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; SAS, sulfasalazine; SB, sleeping beauty; SeMet, selenomethionine; SLC7A11, solute carrier family 7 member 11; SLE, systemic lupus erythematosus; WA, withaferin A.