Classification | Compound | Cell death pathways | Mechanisms | Cancer type | References |
---|---|---|---|---|---|
Small compound | Shikonin | Necroptosis induction | Increases ROS production and upregulates RIPK1, RIPK3, and MLKL | Nasopharyngeal carcinoma | [227] |
FDA-approved drug | FTY720 | Necroptosis induction | Targets I2PP2A/SET and activates PP2A/RIPK1 | Lung cancer | [228] |
NPs | Graphene oxide NPs | Necroptosis induction | Increases the activity of RIPK1, RIPK3, and HMGB1 | Colon cancer | [229] |
NPs | Selenium NPs | Necroptosis induction | Increases ROS and RIPK1 production | Prostate adenocarcinoma cells | [230] |
Small compound | Emodin | Necroptosis induction | Enhances TNF/RIPK1/RIPK3 signaling | Glioma | [231] |
Small compound | Ophiopogonin D′ | Necroptosis induction | Upregulates RIPK1 | Prostate cancer | [232] |
Small compound | Resibufogenin | Necroptosis induction | Upregulates RIPK3 | CRC | [104] |
Small compound | Bufalin | Necroptosis induction | Upregulates RIPK1/RIPK3 | Breast cancer | [233] |
Small compound | Tanshinol A | Necroptosis induction | Increases intracellular ROS and MLKL levels | Lung cancer | [234] |
FDA-approved drug | Chloroquine (CQ) | Necroptosis induction | Upregulates RIPK3 | CRC | [235] |
NPs | Hyaluronic acid -modified, lipid-coated PLGA NPs loaded with mRIP3-pDNA | Necroptosis induction | Upregulates RIPK3 | CRC, breast cancer, melanoma | [235] |
Small compound | CBL0137 | Necroptosis induction | Activate ZBP1 | Liver cancer, breast cancer, colorectal cancer, cervical cancer, melanoma | [236] |
Small compound | Smac mimetics | Necroptosis induction | Antagonizes inhibitor of apoptosis proteins (cIAPs) | Burkitt’s lymphoma | [237] |
NPs | Fe(III)-shikonin supramolecular nanomedicine (FSSN) | Necroptosis/ferroptosis induction | 1. Decreases GSH levels 2. Promotes RIPK1-RIPK3 complex generation | Breast cancer | [238] |
Small compound | Necrosulfonamide (NSA) | Necroptosis inhibition | 1. Inhibits MLKL | Breast cancer | [110] |
Small compound | PK68 | Necroptosis inhibition | 1. Inhibits RIPK1 | Melanoma, lung carcinoma cells | [239] |
Small compound | Necrostatin-1 | Necroptosis inhibition | 1. Inhibits RIPK1 | Colitis-associated CRC | [240] |
FDA-approved drug | Metformin | Pyroptosis induction | 1. Induces GSDMD-mediated pyroptosis by targeting the miR-497-PELP1 axis 2. Causes mitochondrial dysfunction and activates the AMPK/sirtuin1/NF-κB pathway | Breast cancer, esophageal squamous cell carcinoma | |
Small compound | Tetraarsenic hexoxide | Pyroptosis induction | Enhance the production of mitochondrial reactive oxygen species (ROS) by inhibiting phosphorylation STAT3 | Breast cancer | [243] |
FDA-approved drug | Docosahexaenoic acid | Pyroptosis induction | Increases caspase-1 levels and activates GSDMD | Breast cancer | [244] |
Small compound | Polyphyllin VI | Pyroptosis induction | Increases ROS production | NSCLC | |
FDA-approved drug | Simvastatin | Pyroptosis induction | Increases caspase-1 expression | NSCLC | [118] |
Small compound | Galangin | Pyroptosis induction | Increases levels of the GSDME N-terminus | Glioblastoma multiforme | [247] |
Investigational drug | Lobaplatin | Pyroptosis induction | Induces ROS production and JNK phosphorylation | Colon cancer | [248] |
Investigational + FDA-approved drugs | Mirdametinib + Vemurafenib | Pyroptosis induction | Inhibits the MEK/ERK 1/2 pathway and promotes Bim/Bmf-mediated mitochondrial depolarization | Melanoma | [182] |
Small compound | Miltirone | Pyroptosis induction | Inhibits the MEK/ERK 1/2 pathway and promotes ROS accumulation | Hepatocellular carcinoma | [249] |
NPs | Biomimetic nanoparticles | Pyroptosis induction | Induces the mitochondrial damage and activates caspase-3 | Breast cancer | [250] |
NPs | DAC + LipoDDP | Pyroptosis induction | Activates the caspase-3 pathway | Breast cancer | [188] |
NPs | Synthetic RIG-I agonist | Pyroptosis induction | Activates STAT1 and NF-κB | Breast cancer | [251] |
NPs | CXCR4-targeted NPs | Pyroptosis induction | Upregulates caspase-11 and NLPR3 expression | Colorectal cancer | [252] |
NPs | Lip MOF NPs | Pyroptosis induction | Cleaves GSDMD and increases IL-1β levels | Cervical cancer | [253] |
NPs | Arsenic trioxide NPs | Pyroptosis induction | Increases caspase-3 expression | Hepatocellular carcinoma | [254] |
NPs | ROS-responsive polyion complex | Pyroptosis induction | Induces oxidative DNA damage | Breast cancer | [255] |
FDA-approved drug | Paclitaxel | Pyroptosis induction | Activates caspase-3/GSDME | Lung cancer | [256] |
Small compound | Anthocyanin | Pyroptosis induction | Increases caspase-1 levels | Oral squamous cell carcinoma | [257] |
Small compound | JQ-1 | Pyroptosis induction | Activates the NF-κB-NLRP3-caspase-1 pathway | Renal cell carcinoma | [258] |
Investigational drug | Talabostat | Pyroptosis induction | Activates caspase-1 | Cervical cancer, fibrosarcoma, breast cancer | [213] |
Small compound | Ivermectin | Pyroptosis induction | Activates P2X4/P2X7-gated pannexin-1 channel | Breast cancer | [259] |
Small compound | Ophiopogonin B | Pyroptosis induction | Activates caspase-1/GSDMD pathway | Lung cancer | [260] |
Small compound | GW4064 | Pyroptosis induction | Activates caspase-3/GSDME pathway | CRC | [261] |
FDA-approved drug | Doxorubicin | Ferroptosis/pyroptosis induction | Increases lipid ROS levels | HCC, CRC | |
Investigational drug | Anti-GSDMB antibody | Pyroptosis inhibition | Inhibits GSDMB | Breast cancer | [264] |
Small compound | Dimethyl fumarate | Pyroptosis inhibition | Inhibits GSDMD | Breast cancer | [265] |
NPs | Zero-valent iron NPs | Ferroptosis induction | Converts zero-valent iron to Fe(II) and facilitates Fenton reactions | Oral cancer | [266] |
NPs | Fe-CO@Mito-PNBE | Ferroptosis induction | (1) Enhances ROS generation (2) Releases Fe(III)/Fe(II) ions in the TME and triggers the Fenton reaction | Cervical cancer, breast cancer | [267] |
Small compound | IMCA | Ferroptosis induction | Downregulates SLC7A11 expression and reduces cellular cysteine uptake | Colorectal cancer | [268] |
Small compound | Imidazole ketone erastin | Ferroptosis induction | Inhibits system XC− | Diffuse large B cell lymphoma | [269] |
Small compound | Hydrolysis product 4 of open chain epothilone analogs | Ferroptosis induction | Inhibits system XC− | Fibrosarcoma, rhabdomyosarcoma | [270] |
Small compound | ML210 | Ferroptosis induction | Suppresses GPX4 | Melanoma, pancreatic cancer, lung adenocarcinoma, fibrosarcoma, renal cell carcinoma, pancreatic cancer | [271] |
Small compound | ML162 | Ferroptosis induction | Suppresses GPX4 | Fibrosarcoma | [59] |
Small compound | DMOCPTL | Ferroptosis induction | Suppresses GPX4 | Breast cancer | [272] |
Small compound | FIN56 | Ferroptosis induction | Inhibits CoQ10 biosynthesis | Fibrosarcoma | [273] |
Small compound | FINO2 | Ferroptosis induction | Suppresses GPX4 | Fibrosarcoma | [274] |
Small compound | Albiziabioside A derivative | Ferroptosis induction | Suppresses GPX4 | CRC | [275] |
Small compound | Trigonelline | Ferroptosis induction | Decreases GSH levels | Head and neck cancer cells | [276] |
FDA-approved drug | Glutamate | Ferroptosis induction | Inhibits system XC− | Fibrosarcoma | [56] |
NPs | MFC-Gem | Ferroptosis induction | Decrease GSH levels | Pancreatic cancer | [277] |
Small compound | Erianin | Ferroptosis induction | Activates Ca2+/CaM signaling | Lung cancer | [278] |
FDA-approved drug | Etoposide | Ferroptosis induction | Decreases GPX4 levels | Myelogenous leukemia | [279] |
NPs | FePt/MoS2 nanocomposites | Ferroptosis induction | Supplies Fe(II) and accelerates Fenton reactions | Cervical carcinoma, breast cancer | [280] |
FDA-approved drug | Sorafenib | Ferroptosis induction | Inhibits cystine–glutamate antiporter (system XC−) | Fibrosarcoma, Ewing’s sarcoma, lung cancer, osteosarcoma | [281] |
Investigational drug + FDA-approved drug | Siramesine + lapatinib | Ferroptosis induction | Inhibits ferroportin-1 | Breast cancer | [282] |
FDA-approved drug | Cisplatin | Ferroptosis induction | Depletes glutathione (GSH) and inactivates GPX4 | NSCLC, colon cancer | [197] |
FDA-approved drug | Decitabine | Ferroptosis induction | Decreases GSH levels and inhibits GPX4 activity | Myelodysplastic syndrome | [283] |
Synthetic exosomes | Erastin@FA-exo | Ferroptosis induction | Suppresses GPX4 expression and upregulates cysteine dioxygenase | Breast cancer | [284] |
FDA-approved drug | Apatinib | Ferroptosis induction | 1. Inactivates GPX4 2. Upregulates ELOVL6/ACSL4 3. Inhibits the VEGFR2/Nrf2/Keap1 pathway | Gastric cancer, colorectal cancer, glioma | |
FDA-approved drug | Altretamine | Ferroptosis induction | Inactivates GPX4 | Diffuse large B cell lymphoma | [288] |
FDA-approved drug | Neratinib | Ferroptosis induction | Increases ferritin levels | Breast cancer | [289] |
Investigational drug | APR-246 | Ferroptosis induction | Decreases GSH biosynthesis | Acute myeloid leukemia | [290] |
Investigational drug | Flubendazole | Ferroptosis induction | Inhibits SLC7A11 transcription | Prostate cancer | [291] |
FDA-approved drug | Sulfasalazine | Ferroptosis induction | Inhibits system XC− | Head and neck cancer | [292] |
FDA-approved drug | Statins | Ferroptosis induction | Inhibits CoQ10 biosynthesis | NSCLC | |
FDA-approved drug | Dihydroartemisinin | Ferroptosis induction | Inhibits GPX4 | Leukemia | |
Small compound | RSL3 | Ferroptosis induction | Suppresses GPX4 | CRC | [297] |
Small compound | MMRi62 | Ferroptosis induction | Degrades mutant p53 and ferritin heavy chain | Pancreatic cancer | [298] |
FDA-approved drug | Artesunate | Ferroptosis induction | Promotes ROS signaling and lipid peroxidation | Pancreatic cancer | [299] |
Investigational drug | Buthionine sulfoximine | Ferroptosis/cuproptosis induction | Decreases GPX4 levels | Hepatocellular carcinoma, lung cancer | |
Small compound | 5-aminolevulinic acid | Ferroptosis induction | Inhibits GPX4 and increase heme oxygenase 1(HO-1) | Esophageal squamous cell carcinoma | [301] |
Chinese patent medicine | Shuganning injection | Ferroptosis induction | Increases HO-1 | Triple-negative breast cancer | [302] |
Small compound | Trichothecin | Ferroptosis induction | Upregulates RIPK3 | CRC, Burkitt lymphoma | [303] |
NPs | ZVI-NP | Ferroptosis induction | Inactivates NRF2 | Lung cancer | [194] |
NPs | 2,2,6,6, tetramethylpiperidine-N-oxyl capped TiO2 nanorods (TiO2 NRs) + radiotherapy | Ferroptosis inhibition | Induces GSH | Breast cancer | [304] |
Small compound | Liproxstatin-1 | Ferroptosis inhibition | Slow the accumulation of lipid hydroperoxides | Pancreatic cancer | [305] |
Investigational drug | Elesclomol | Cuproptosis induction | 1. Increases copper levels and targets lipoylated TCA cycle proteins 2. Targets copper-transporting ATPase 1 and regulates ferroptosis | NSCLC, lung adenocarcinoma, pancreatic cancer, papillary thyroid carcinoma, ovarian cancer, colorectal cancer | |
NPs | CuET NPs | Cuproptosis induction | Reduces FDX1 expression | NSCLC | [306] |