C18

C18 is a covalent inhibitor of glutathione peroxidase 4 (GPX4; IC₅₀ = 120 nM).¹ It inhibits the growth of MDA-MB-468, BT-549, and MDA-MB-231 breast cancer cells (IC₅₀s = 10, 75, and 12 nM, respectively). C18 (10 and 20 µM) increases lipid peroxidation and oxidized malondialdehyde (MDA) levels in MDA-MB-231 cells, an effect that can be prevented by the ferroptosis inhibitor ferrostatin-1 (Item No. 17729). It decreases mitochondrial volume and induces degradation of mitochondrial crests and outer membranes in MDA-MB-231 cells when used at a concentration of 20 µM. In vivo, C18 (5, 10, or 20 mg/kg) reduces tumor volume and weight, without affecting body weight, in an MDA-MB-231 mouse xenograft model.

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1. Chen, T., Leng, J., Tan, J., et al. Discovery of novel potent covalent glutathione peroxidase 4 inhibitors as highly selective ferroptosis inducers for the treatment of triple-negative breast cancer. J. Med. Chem. 66(14), 10036-10059 (2023).