Ferroptosis: Opportunities and Challenges in Myocardial Ischemia-Reperfusion Injury

Table 1

Small molecules, drugs, and ferroptosis.

Small molecules or drugs	Intervention target	Molecular weight	Molecular formula	Function	Experimental cells/animals	References
Erastin	VDAC 2/3 or system Xc^-	547.04	C30H31ClN4O4	Prevents cystine import, causes GSH exhaustion,cause ferroptosis	BJeLR HT1080 143B p^° and p^+ cell U2OS DU-145	[1, 9, 10, 51, 88]
RSL3	GPX-4	440.9	C23H21ClN2O5	Covalent inhibitor of GPX-4 that causes accumulation of lipid hydroperoxides and ferroptosis	KBM7 MIA PaCa-2 A549, Calu-1, HCT116, HT1080 BJeLR	[10, 89]
Buthionine sulfoximine	GSH exhaustion	222.305	C8H18N2O3S	Cause ferroptosis	BJeLR; HCT116/A549	[51]
Acetaminophen	GSH exhaustion	151.163	C8H9NO2	Cause ferroptosis	HepG2/primary mouse	[90]
Sulfasalazine	System Xc^-	398.394	C18H14N4O5S	Low potency inhibitor that prevents cystine import, causes GSH depletion and ferroptosis	BJeLR/HT1080 HT1080/Calu-1	[1, 51]
Sorafenib	System Xc^-	464.825	C21H16ClF3N4O3	Cause ferroptosis	HT1080/Calu-1DU-145 nude mice	[51, 91–93]
Artesunate	—	384.421	C19H28O8	Cause ferroptosis	PDAC cell lines	[94]
Piperazine erastin	VDACs or system Xc^-	645.19	C35H41ClN6O4	Cause ferroptosis	BJeLR nude mice	[88]
Trolox	Lipophilic antioxidants	250.29	C14H18O4	Blocks propagation of lipid peroxidation, may inhibit lipoxygenases, inhibiting ferroptosis	HT1080/PUFA oxidation-induced death model on S. cerevisiae	[1, 95]
Ebselen	Oxidative pathway	274.17666	C13H9NOSe	Inhibiting ferroptosis	HT1080, Calu-1	[1]
SSRS 11-92	ROS from lipid peroxidation	—	—	Inhibiting ferroptosis	HD model	[95]
α-Tocopherol (vitamin E)	Oxidative pathway	430.71	C29H50O2	Blocks propagation of lipid peroxidation, may inhibit lipoxygenases, inhibitting ferroptosis	BReLR GPX4-deficient T-cell mice	[10, 96]
Deferoxamine	Fenton reaction	560.68	C25H48N6O8	Depletes iron and prevents iron-dependent lipid peroxidation, inhibiting ferroptosis	Wild-type and Bax/Bak	[1]
Deferoxamine mesylate (DFO)	Intracellular iron	656.8	C25H48N6O8•CH4O3S	Inhibiting ferroptosis	BJeLR	[10]
SRS 16-86	ROS from lipid peroxidation	432.2525	C16H24N2O2	Inhibiting ferroptosis	HT1080/NIH 3T3 IRI mice model	[97]
Ferrostatin-1 (Fer-1)	ROS from lipid peroxidation	262.35	C15H22N2O2	Blocks lipid peroxidation, inhibiting ferroptosis	HT1080	[1, 95]
Liproxstatin-1 (Lip-1)	ROS from lipid peroxidation	340.85	C19H21ClN4	Blocks lipid peroxidation, inhibiting ferroptosis	HRPTEpiCs GPX4^−/− cells; GPX4^−/− mice	[98]