Table 2.

Genetic and pharmacologic inhibitors of ferroptosis.

Target	Effector/reagent	Proposed mechanism	Reference(s)
Genetic inhibitors
SLC7A11	NRF2	Activates antioxidant genes; Upregulates SLC7A11	[127]
NRF2	KEAP1	Stabilizes and regulates NRF2	[127]
Lipid peroxides	GPX4	Eliminates phospholipid hydroperoxides	[17, 103]
Lipid peroxides	TXNRD1	Eliminates phospholipid hydroperoxides	[55]
Cystine	SLC7A11	Component of system Xc-; Antiporter for cystine	[14, 17]
System Xc-	CD44v	Binds to SLC7A11 to stabilize system Xc-	[128]
Actin dynamic	HSPB1	Regulates iron uptake and GPX4 abundance	[129]
Iron storage	FTH1	Subunit of intercellular iron-storage protein	[127, 130, 131]
Iron metabolism	STEAP3	Metalloreductase converting Fe3+ to Fe2+	[132]
Iron transport	FPN	Exports iron and reduces intercellular iron accumulation	[28, 133]
Iron transport	CISD1	Inhibits mitochondrial iron uptake and respiratory capacity	[34]
Iron metabolism genes	FANCD2	Regulates iron metabolism and lipid peroxidation	[132]
BH4 synthesis	GCH1	Involved in BH4 synthesis	[60, 61]
S-adenosyl homocysteine hydrolase	DJ-1	Determines the formation of the S-adenosyl homocysteine hydrolase tetramer and its enzymatic activity	[134]
CoQ10	FSP1	Converts CoQ10 to CoQ10H2, reducing membrane phospholipid peroxidation	[15, 16]
CoQ10	DHODH	Converts CoQ10 to CoQ10H2 in mitochondrial	[63]
PI3K-AKT-mTOR signaling pathway	mTORC1	Regulates amino acid metabolism and upregulates SREBP1/SCD1-mediated lipogenesis	[23]
SHP1-NF-κB- LCN2	LIFR	Suppresses NF-κB signaling through SHP1, leading to downregulation of LCN2	[99]
Pharmacologic inhibitors
Iron chelators	Deferoxamine, deferoprone, deferasirox, cyclipirox	Chelate iron and block iron-dependent lipid peroxidation	[17, 135]
Lipophilic antioxidation	Fer-1, Lip-1, UAMC-3203, TEMPO, MitoTEMPO, α-tocopherol, trolox, BTH, CoQ10, idebenone, BH4, bazedoxifene, 2-(1-(4-(4-methylpiperazin-1-yl)phenyl)ethyl)-10H-phenothiazine	Inhibit lipid peroxidation	[4, 15–17, 23, 61, 115, 136]
LOX inhibitors	Zileuton, AA-861, PD-146176	Suppress LOXs and blocks LOX-induced lipid peroxidation	[111, 113, 137]
Amino acid metabolism	Glutathione, N-acetylcysteine, β-mercaptoethanol	Recover intracellular cysteine	[17]
Lipid peroxidation	Deuterated polyunsaturated fatty acids (D-PUFAs)	Suppress the initiation and propagation of lipid peroxidation	[138]
Protein synthesis	Cycloheximide	Blocks ferroptosis induced by system Xc-	[17]
GPX4	PKUMDL-LC-101-D04	Activates GPX4 by allosteric activity	[117]
ACSL4	Rosiglitazone, pioglitazone, troglitazone	Inhibits ACSL4	[41]
DPP4	Vildagliptin, linagaliptin, alogliptin	Suppress DPP4-dependent lipid peroxidation	[67]
Selenoproteins	Selenium, methylselenocysteine, selenocystamine	Replenishes of GPX4 and other selenoproteins	[56, 139, 140]
N/A	Necrostatin-1, necrostatin-1f	Suppress ferroptosis in a RIPK1-independent manner	[4, 114]

ACSL4 acyl-CoA synthetase long-chain family member 4, AKT AKT serine/threonine kinase, BTH butylated hydroxytoluene, BH₄ tetrahydrobiopterin, CD44v CD44 variant, CISD1 CDGSH iron-sulfur domain‒containing protein 1, CoQ₁₀ ubiquinone, CoQ₁₀H₂ ubiquinol, DHODH dihydroorotate dehydrogenase, DPP4 dipeptidyl peptidase-4, FANCD2 Fanconi anemia complementation group d2, Fer-1 ferrostatin-1, FPN ferroportin, FTH1 ferritin heavy chain 1, FSP1 ferroptosis suppressor protein 1, GCH1 guanosine triphosphate cyclohydrolase 1, GPX4 glutathione peroxidase 4, HSPB1 heat shock protein b1, KEAP1 kelch like ECH associated protein 1, LCN2 lipocalin 2, LIFR leukemia inhibitory factor receptor, Lip-1 liproxastatin-1, LOX lipoxygenases, mTORC1 mechanistic target of rapamycin complex 1, NRF2 nuclear factor erythroid 2-related factor 2, PI3K phosphoinositide-3-kinase, RIPK1 receptor interacting protein kinase 1, SCD1 stearoyl-CoA desaturase, SHP1 SH2-containing protein tyrosine phosphatase, SLC7A11 solute carrier family 7 member 11, SREBP1 sterol regulatory element-binding protein 1, STEAP3 six-transmembrane epithelial antigen of prostate 3, TXNRD1 thioredoxin reductase 1, N/A not applicable.