Table 1.
Key ferroptosis inducers in tumor therapy
| Name | Mechanisms | IC50 | Models | Note | References |
|---|---|---|---|---|---|
| Experimental compounds | |||||
| Erastin | Inhibits system xc- | 1.2 μM in HT1080 | Various cancer cell lines, especially BJ-TERT/LT/ST/RASV12, HT1080 and Calu-1 | [4] | |
| Erastin2 | Inhibits system xc- | 0.15 µM in HT1080 | HT1080 and Calu-1 | [23] | |
| Imidazole ketone erastin (IKE) | Inhibits system xc- | 3 nM in BJ-TERT/LT/ST/RASV12 | BJ-TERT/LT/ST/RASV12, HT1080 and Calu-1; xenograft model; orthotopic model | Metabolically stable inhibitor of system xc-, potentially suitable for in vivo applications | [24] |
| L-Buthionine-(S,R)-Sulfoximine (BSO) | Inhibits GCLC | 26.5 µM in MCF-7 | Various cancer cell lines, especially HT1080 and Calu-1 | BSO alone may not be sufficient to induce ferroptosis in certain cancers | [4, 25] |
| RSL3 | Inhibits GPX4 | 100 nM in Pfa1 | Various cancer cell lines, especially HT1080 and Calu-1; xenograft model | It has off-target effects on TXNRD1 | [4, 26] |
| ML162 | Inhibits GPX4 | 25 nM in BJ-TERT/LT/ST/RASV12 | Various cancer cell lines, especially BJ-TERT/LT/ST/RASV12, HT1080 and Calu-1 | It has off-target effects on TXNRD1 | [26–28] |
| ML210 | Inhibits GPX4 | 71 nM in BJ-TERT/LT/ST/RASV12 | Various cancer cell lines, especially BJ-TERT/LT/ST/RASV12, HT1080 and Calu-1 | [27] | |
| JKE-1674 | Inhibits GPX4 | 0.03 µM in LOX-IMVI | Various cancer cell lines, especially HT1080 and LOX-IMVI | Active metabolite of ML210 | [27] |
| JKE-1716 | Inhibits GPX4 | N/A | Various cancer cell lines, especially HT1080 and LOX-IMVI | Derivative of ML210 | [27] |
| FIN56 | Inhibits GPX4 | 5 µM in HT1080 | Various cancer cell lines, especially HT1080 | It also binds to and activates FDFT1/SQS | [29] |
| FINO2 | Inhibits GPX4 | 5.8 µM in HT1080 | Various cancer cell lines, especially HT1080 | Oxidizes iron, resulting in the loss of GPX4 enzymatic activity | [30] |
| iFSP1 | Inhibits AIFM2/iFSP1 | 3 µM in Pfa1 | GPX4-knockout Pfa1 and HT1080 cells that overexpresses AIFM2 | iFSP1 alone may not be sufficient to induce ferroptosis in certain cancers | [12] |
| icFSP1 | Inhibits AIFM2/iFSP1 | 30 µM in HT1080 | Human cancer cells (H460, A375, and HT1080 cells); xenograft model | It indirectly inhibits AIFM2/FSP1 by inducing condensate formation | [14] |
| Torin 1 | Inhibits MTOR | 10 nM (cell free system) | UMRC6 | [31] | |
| ZZW-115 | Inhibits NUPR1 | 2.1 µM in PANC1 | PANC1, MiaPaCa-2 and HepG2 | [32, 33] | |
| Alkaloid trigonelline | Inhibits NFE2L2 | N/A | HepG2, Hepa1–6, Hep3B, and SNU-182; xenograft model | [34] | |
| Brequinar | Inhibits DHODH | 20 nM (cell free system) | Various cancer cell lines, especially NCI-H226 and HT1080cells | It has off-target effects on AIFM2 | [13] |
| MF-438 | Inhibits SCD/SCD1 | 2.3 nM (cell free system) | KYSE30, KYSE70, KYSE140, KYSE150, KYSE410, KYSE450, KYSE510 and SHEE cells | [35] | |
| N6F11 | Activates TRIM25 | 5 µM in PANC1 | Various cancer cell lines, especially PANC1 | Induces TRIM25-dependent GPX4 degradation in cancer cells | [36] |
| Clinical drugs | |||||
| Sulfasalazine | Inhibits system xc- | 5 mM in HT1080 | Various cancer cell lines, especially HT1080 and Calu-1 | An anti-inflammatory drug structurally related to salicylates. It is indicated for managing inflammatory diseases such as ulcerative colitis and rheumatoid arthritis | [37] |
| Sorafenib | Inhibits SLC7A11 | 4.5 µM in HepG2 | Various cancer cell lines, especially HT1080 and HepG2; xenograft model | A kinase inhibitor used to treat unresectable liver carcinoma, advanced renal carcinoma, and differentiated thyroid carcinoma; Sorafenib may not trigger ferroptosis in certain cancer types | [37, 38] |
| Statins (lovastatin, simvastatin) | Inhibit HMG-CoA reductase | Lovastatin: 1.4 nM simvastatin: 0.12 nM (cell free system) | HT1080 and Calu-1 | A class of lipid-lowering medications | [29, 39] |
| Artemisinin | Increases iron accumulation | 20.36 nM (cell free system) | Various cancer cell lines, especially NCI-H292 and HCT116 | It is used to treat malaria | [40] |
| Artesunate | Increases iron accumulation | 1.28 nM (cell free system) | Various cancer cell lines, especially HT1080 and Calu-1 | It is used to treat malaria | [41] [42] |
| Rapamycin | Inhibits MTOR | 0.5 ng/ml in rhabdomyosarcoma cells | PANC1 | An immunosuppressive agent | [43] |
| Abemaciclib | Inhibits CDK4/6 | 10 nM (cell free system) | ER+ breast cancer cell lines; xenograft model | It is used to treat is used to treat certain types of breast cancer known as HR+/HER2– | [44] |
| Disulfiram | Induces mitochondrial damage | 0.1 mM (cell free system) | GBM U251 and LN229 | It is used to treat chronic alcoholism | [45] |
| Doxorubicin | Increases PUFA | 40 µM (cell free system) | Cardiomyocytes | They are chemotherapy medicines used to treat certain types of cancer | [46] |
| Oxaliplatin | Induces ROS production | 2.7 µM in KB-CP20 | HT29 and KB-CP20 | An alkylating agent used to treat certain types of cancer | [47] |
| Cisplatin | Induces GSH depletion | 2 µM in HOS | A549, HOS and HCT116 | An alkylating agent used to treat certain types of cancer | [48] |
| Lapatinib | Increases iron accumulation | 10.8 nM (cell free system) | MDA MB-231 | A tyrosine kinase inhibitor used for the treatment of advanced or metastatic HER2+ breast cancer | [49] |
| Neratinib | Increases iron accumulation | 92 nM (cell free system) | TBCP-1 and SKBR3; xenograft model | A tyrosine kinase inhibitor used for the treatment of advanced or metastatic HER2+ breast cancer | [49] |
| Zalcitabine | Induces mitochondrial DNA stress | 20 µM in PANC1 | PANC1 and Capan2; xenograft model | A dideoxynucleoside antiretroviral agent used for the treatment of human immunodeficiency virus | [50] |