Table 1.
Main inducers of iron-dependent cell death
| Small molecules | Cell death | Targets/MoA | Preclinical models | References |
|---|---|---|---|---|
| Erastin | Ferroptosis | Irreversibly inhibits system xc- | BJ, TIP5 transformed cell lines | (Dixon et al., 2012; Dolma et al., 2003) |
| Imidazole ketone erastin (IKE) | BJ transformed cell lines, DLBCL xenografts model | (Larraufie et al., 2015; Zhang et al., 2019) | ||
| Sulfasalazine | Lymphoma cell lines | (Gout et al., 2001) | ||
| L-buthionine sulfoximine (BSO) | Sensitizes to ferroptosis | Inhibits γ-glutamylcysteine synthetase (γ-GCS) and GSH production | Not defined | (Griffith and Meister, 1979) |
| Piperlongumine (PL) | Ferroptosis | Acts partly by modulating GSH levels | Various in vitro and in vivo models including pancreatic cancer | (Tripathi and Biswal, 2020; Yamaguchi et al., 2018) |
| Phenethylisocyanate (PEITC) | Sensitizes to ferroptosis | Various in vitro and in vivo models including ovarian and pancreatic cancer | (Kasukabe et al., 2016; Trachootham et al., 2006) | |
| ML162 | Ferroptosis | Inhibits GPX4 | BJ transformed cell line | (Weiwer et al., 2012) |
| RSL3 | BJ transformed cell line | (Yang et al., 2014; Yang and Stockwell, 2008) | ||
| Masked nitrile-oxides (e.g., ML210) and propiolamides | Various cancer cell lines including melanoma, renal, fibrosarcoma, colon, pancreatic cancers | (Eaton et al., 2020a; Eaton et al., 2020b) | ||
| iFSP1 | Synergizes with RSL3-and dimethyl fumarate-induced ferroptosis | Inhibits FSP1 | Various cancer cell lines including DLBCL cell lines | (Doll et al., 2019; Schmitt et al., 2021) |
| Brequinar | Ferroptosis in GPX4low cells | Inhibits DHODH and synergizes with sulfasalazine in GPX4high cells | Various in vitro and in vivo models including fibrosarcoma and lung squamous cell carcinoma | (Mao et al., 2021) |
| Fin56 | Ferroptosis | Promotes GPX4 degradation and activates squalene synthase | BJ transformed cell lines | (Shimada et al., 2016) |
| FINO2 | Promotes iron oxidation and indirect inhibition of GPX4 | BJ transformed cell line, fibrosarcoma | (Abrams et al., 2016; Gaschler et al., 2018) | |
| Ferroptocide | Inhibits thioredoxin | Various cancer cell lines and primary cancer cells | (Llabani et al., 2019) | |
| Methotrexate | Synergizes with GPX4 inhibition to induce ferroptosis | Inhibits dihydrofolate reductase | Jurkat cells | (Soula et al., 2020) |
| Salinomycin, ironomycin | Lysosomal cell death | Sequester lysosomal iron | HMLER transformed cell line, breast cancer xenografts | (Mai et al., 2017; Muller et al., 2020) |