GPX4 Inhibitor A16

GPX4 Inhibitor A16 may be used in proteomics research to study GPX4 function in in situ and in vivo conditions and explore the therapeutic potential of pancreatic cancer via ferroptosis induction.

GPX4 Inhibitor A16, equipped with a cysteine reactive warhead ynamide, is a highly potent and selective covalent inhibitor of glutathione peroxidase 4 (GPX4), surpassing existing inhibitors like ML210 and ML162 in its ability to induce ferroptosis in cancer cells through GPX4 inhibition. With its wide-ranging effectiveness across various cell lines (IC50: 0.02-0.2 μM) and significant in vivo (10 mg/kg, i.p., in AsPC-1 xenograft mouse model) anticancer activity coupled with a favorable safety profile, A16′s mechanism, verified by chemical proteomics and ferrostatin-1 rescue assays, demonstrates its considerable therapeutic potential by targeting the GPX4-dependent ferroptosis pathway.