[4-[Bis(4-chlorophenyl)methyl]piperazin-1-yl]-(5-methyl-4-nitro-1,2-oxazol-3-yl)methanone

ML210 (CAS 1360705-96-9) 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

ML 210 has been used as a glutathione peroxidase 4 (GPX4) inhibitor to induce ferroptosis in cancer cells. It has also been used as a GPX4 inhibitor to examine whether pharmacological inhibition of GPX4 altered prominin2 expression and impacted ferroptosis in adherent MCF10A and Hs578t cells.

ML 210 induces non-apoptotic cell death in tumor cells expressing the RAS oncogene.

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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