ML210
GPX4 inhibitor / Ferroptosis inducer / ML210 is selectively synthetic lethal to HRAS expressing cells compared to isogenic non-HRAS cells (IC50 = 7.1 nM for BJeLR (expressing HRASg12v) cells vs IC50 = 272 nM for BJeH-LT (non-HRAS expressing) cells.1 ML210 is able to inhibit glutathione peroxidase 4 (GPX4), an important selenoenzyme that protects cells from ferroptosis caused by iron catalyzed formation of free radicals from lipid peroxides.2,3 Treatment of several treatment-resistant cancer cell lines exhibiting a high mesenchymal state with ML210 resulted in selective induction of ferroptosis.3
Biochemicals & reagents
1360705-96-9
1) Weiwer et al. (2012), Development of small-molecule probes that selectively kill cells induced to express mutant RAS; Bioorg.Med.Chem.Lett. 22 1822 2) Yang et al. (2014), Regulation of Ferroptotic Cancer Cell Death by GPX4; Cell 156 317 3) Viswanathan et al. (2017), Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway; Nature 547 453
RT
TARGET: Glutathione -- PATHWAY: Ferroptosis; Mitochondrial function; Redox -- RESEARCH AREA: Cell death; Oxidative stress -- DISEASE AREA: Cancer