TABLE 2.

FDA-approved synthetic drugs associated with ferroptosis.

Drugs	Functional targets	Impact on ferroptosis	Diseases	Test models	Mechanisms/Effects	Refs
Sulfasalazine (SAS)	System xc -	Induce	Fibrosarcoma; Breast cancer; Pancreatic cancer	MDA-MB-231, T47D, BT549, MCF7, CFPAC1 cells; PANC1, HT-1080 cells and xenograft mice; Panc02 orthotopic mice	GSH depletion; SLC7A11 downregulation; Lipid peroxidation	Dixon et al. (2012), Zhu et al. (2017), Wang W. et al. (2019), Yu et al. (2019)
Sorafenib	System xc -	Induce	Hepatocellular carcinoma (HCC)	HepaG2, Hep3B cells; Hepatocytes from HCC patients	Lipid peroxidation; GSH depletion; Increasing ROS level	Lachaier et al. (2014), Sun et al. (2016a), Sun et al. (2016b)
Lanperisone	System xc -	Induce	K-ras-driven tumors	K-ras-mutant mouse embryonic fibroblasts (MEFs) and xenograft mice	GSH depletion; Increasing ROS level	Shaw et al. (2011)
Glutamate; Glutamine	System xc -	Induce	Fibrosarcoma	OHSCs, MEFs; HT-1080, HT22 cells; Primary cortical neurons	Inhibiting cystine import; GSH depletion	Dixon et al. (2012), Gao et al. (2015), Bueno et al. (2020)
Statins (fluvastatin, simvastatin, lovastatin acid)	GPX4	Induce	Fibrosarcoma	HT-1080 cells	Downregulating GPX4 level, mevalonate pathway and selenoprotein biosynthesis; Lipid peroxidation	Viswanathan et al. (2017)
Altretamine	GPX4	Induce	DLBCL	OCI-LY3, OCI-LY7, U-2932 cells	GPX4 inactivation; Decreased PC-OOH level; Lipid ROS accumulation	Woo et al. (2015)
Ferumoxytol (Feraheme)	Iron	Induce	Leukemia	19 kinds of leukemia cells; PDXs of leukemia cells	FPN downregulation; Increasing intracellular iron and ROS levels	Trujillo-Alonso et al. (2019)
Salinomycin (ironomycin)	Iron	Induce	Breast cancer	Human breast cancer stem cells (CSCs); PDXs	Iron accumulation and sequestration in lysosomes; Degraded ferritin, the iron storage protein; Increasing ROS and TFRC	Mai et al. (2017)
Ferric ammonium citrate (FAC)	Iron	Induce	Fibrosarcoma	HT-1080 cells	Iron overloading; Oxidative damage; Activating ALOXs; Increasing ROS production	Fang et al. (2018)
Cisplatin	GSH	Induce	NSCLC; Human colon cancer	A549, HCT116 cells	GSH depletion; Increasing ROS level; Inducing both ferroptosis and apoptosis	Guo et al. (2018a), Guo et al. (2018b)
Haloperidol	Sigma 1 receptor	Induce	HCC	HepG2, Huh-7 cells	Increasing cellular levels of HO-1	Bai et al. (2017)
Busulfan	NRF2; GPX4	Induce	—	Oligospermia mice	Downregulating expressions of NRF2, GPX4 and FPN	Zhao et al. (2020)
Siramesine and lapatinib	Iron; FPN	Induce	Breast cancer	MDA-MB-231, SKBR3 cells	Iron and ROS accumulation; Upregulating TF; Downregulating FPN and ferritin	Ma et al. (2017)
Ciclopirox olamine (CPX)	Iron	Inhibit	Neuro-degenerative diseases	HT1080 cells; OHSCs	Removing excess iron; Rescuing cells from erastin-induced ferroptosis	Dixon et al. (2012)
Deferoxamine (DFO)	Iron	Inhibit	Neuro-degenerative diseases; Ageing	HT-1080, Calu-1, BJeLR, PC12, MEF cells; Ageing model mice	Removing excess iron; Rescuing from erastin-induced ferroptosis	Dixon et al. (2012), Chen X. et al. (2020)
Dexrazoxane (DXZ)	Iron	Inhibit	Cardiomyopathy	DOX-induced cardiomyopathy model mice; Acute and chronic I/R model mice	Reducing DOX- cardiomyopathy; Maintaining mitochondrial function	Fang et al. (2019)
Deferiprone (DFP)	Iron	Inhibit	Neuro-degenerative diseases	Primary hippocampal neurons and hippocampus of developing rats and aged mice after general anaesthesia	Iron depletion; Slowing disease progression and improving motor function; Protecting cells against ferroptosis	Wu et al. (2020)
Thiazolidinediones (TZDs) Rosiglitazone pioglitazone troglitazone	ACSL4	Inhibit	Intestinal and pulmonary I/R	ACSL4-knockout MEFs GPX4-knockout mice; Caco-2 cells; Intestinal and pulmonary I/R model mice; Hypoxia-reoxygenation (HR) model A549 cells	Inhibiting ACSL4 and COX2 expression; Restoring GPX4 expression Inhibiting lipid peroxidation and ferroptosis; Improving tissue death	Doll et al. (2017), Li Y. et al. (2019), Xu et al. (2020)
N-acetylcysteine (NAC)	ALOX5	Inhibit	Hemorrhagic stroke	HT-1080 cells; Primary cortical neuronal cultures; ICH model mice and rats	Increasing GSH; Inhibiting active lipids; Neutralizing toxic lipids	Dixon et al. (2012), Karuppagounder et al. (2018)
Zileuton	ALOX5	Inhibit	Neuro-degenerative diseases; Iron overload related diseases	Molt-4, Jurket, HT22, HT-1080 cells	Decreasing ROS production; Rescuing from glutamate oxidative toxicity; Neuroprotective effect	Liu et al. (2015), Probst et al. (2017), Fang et al. (2018)
Vildagliptin; Alogliptin; Linagliptin	DPP4	Inhibit	—	TP53+/+ and TP53−/− HCT116 cells and mice	Blocking DPP4-mediated lipid peroxidation; Attenuating the anticancer activity of erastin on TP53−/−CRC cells	Xie et al. (2017)
Dopamine	Neuro-transmitter	Inhibit	Neuro-degenerative diseases	HT-22, HT-1080, PANC-1, HEY, HEK293, MEF cells	Reducing GSH depletion; Increasing GPX4, iron accumulation and MDA production; Protecting cells against lipid peroxidation	Wang D. et al. (2016), Tang and Tang, (2019)
Cycloheximide (CHX)	Protein synthesis	Inhibit	Neuro-degenerative diseases	HT1080, Calu-1, BJeLR, MEF cells	Inhibiting protein synthesis; Preventing erastin-induced ferroptosis	Dixon et al. (2012)
Tocotrienols: Vitamin E; α-tocopherols	Lipid peroxidation	Inhibit	Acute lymphocytic chorio-meningitis virus and Leishmania major parasite infections; Hepatic I/R	HT-1080, BJeLR cells; GPX4-deficient T cells and mice; Hepatic I/R model mice	Eliminating peroxygen free radicals; Preventing lipid peroxidation	Yang et al. (2014), Matsushita et al. (2015), Yamada et al. (2020a)
Coenzyme Q10 (CoQ10); Idebenone	Mevalonate pathway	Inhibit	—	Four engineered BJ cell lines (BJeLR, DRD, BJeHLT, BJeH); HT-1080 cells	Inhibiting ROS production	Shimada et al. (2016a)
α-Lipoic acid	Unknown	Inhibit	Alzheimer’s disease (AD)	P301S Tau transgenic mice	Increasing FPN, xCT and GPX4; Decreasing TFRC, iron and ROS generation	Zhang Y. -H. et al. (2018)