Copyright ©The Author(s) 2022.
World J Gastrointest Oncol. Jan 15, 2022; 14(1): 1-18
Published online Jan 15, 2022. doi: 10.4251/wjgo.v14.i1.1
Table 1 Common ferroptosis inducers
System Xc-ErastinInhibits the activity of System Xc- and affects the synthesis of GSH; binds to VDAC2/3 to induce mitochondrial dysfunction[3,6]
Erastin analogs, piperazine erastin, imidazole ketone erastinInhibits the activity of System Xc- and affects the synthesis of GSH[103,104]
SulfasalazineInhibits the activity of System Xc- (weaker inhibitory effect than erastin) [3,105,106]
SorafenibInhibits the activity of System Xc- (directly affects the synthesis of GSH in a narrow concentration range)[107]
GlutamateInhibits the activity of System Xc-, high extracellular glutamate concentrations prevent cystine import[3,7]
GPX4(1S,3R)-RSL3Covalently binds to the selenocysteine residue of GPX4[5,26]
DPI7 (ML162), DPI12, DPI17Covalently bind to GPX4 (at the same binding site as RSL3)[7,26]
DPI10 (ML120), DPI13Indirectly inhibit GPX4 activity or bind to a site different from RSL3[26,103]
FIN56Induces GPX4 degradation; binds and activates SQS to deplete CoQ10[108]
AltretamineInhibits the activity of GPX4[64]
GSHBSO GSH depletion[7,103]
CisplatinBinds to GSH to inactivate GXP4[109]
DPI2Depletes GSH[7,103]
CysteinaseDepletes cysteine, resulting in GSH depletion[7]
PiperlongumineDepletes GSH and inhibits the activity of GXP4[7,64]
ROS and ironFINO2Oxidizes Fe2+ ions and promotes intracellular accumulation of ROS; indirectly inactivates GPX4; directly oxidizes PUFAs[110]
Ferric ammonium citrateIncreases iron abundance[7]
Silica-based nanoparticlesDelivers iron into cells and reduce GSH abundance[7]
HemeUpregulates HMOX1 expression and increases the intracellular level of labile iron[111]
ART, DHAOxidize Fe2+ ions and promote intracellular accumulation of ROS; induce ferritinophagy and the release of labile iron[7,51,65]
Siramesine and lapatinibDownregulate FPN expression and upregulate TRF expression to increase intracellular labile iron levels[112]
Table 2 Common ferroptosis inhibitors
Lipid peroxidationVitamin E, α-tocopherol, trolox, tocotrienolsBlock propagation of lipid peroxidation, may inhibit lipoxygenases[7]
Deuterated polyunsaturated fatty acids Block initiation and propagation of lipid peroxidation[7]
Butylated hydroxytoluene, butylated hydroxyanisoleBlock lipid peroxidation[7]
Ferrostatins, liproxstatinsScavenge ROS and inhibit lipid peroxidation; regulate the expression of oxidation-related proteins[7]
CoQ10, idebenoneBlock lipid peroxidation[7]
Baicalein, PD-146176, AA-861, zileutonBlock lipoxygenase-induced lipid peroxidation[7]
TroglitazoneSpecifically inhibits ACSL4[12]
ZileutonSpecifically inhibits LOX[113]
Vildagliptin, alogliptin, linagliptinBlock DPP4-mediated lipid peroxidation[7,49]
IronDeferoxamine, cyclipirox, deferiproneDeplete iron and prevent iron-dependent lipid peroxidation[7]
Nitrogen oxidesBlock the Fenton reaction and inhibit the production of hydroxyl radicals[114]
CurcuminChelates iron to reduce iron accumulation; activates the Nrf2 signaling pathway[115]