GPX4 inhibitor 17 is a ferrocene-containing inhibitor of glutathione peroxidase 4 (GPX4) and an inducer of ferroptosis.1 It inhibits GPX4 activity by 49.16% when used at a concentration of 1 ?M. GPX4 inhibitor 17 (0.5 ?M) increases the production of reactive oxygen species (ROS) and levels of malondialdehyde (MDA) in OS-RC-2 clear cell renal cell carcinoma cells. It induces ferroptosis in HT-1080 cells (IC50s = 0.007 and 1.486 ?M, in the absence and presence of ferrostatin-1, respectively). GPX4 inhibitor 17 (20 mg/kg) reduces tumor volume and intratumoral GPX4 levels in an OS-RC-2 mouse xenograft model.
References:
[1]. Li, W., Yu, J., Wang, J., et al.How does ferrocene correlate with ferroptosis Multiple approaches to explore ferrocene-appended GPX4 inhibitors as anticancer agentsChem. Sci.15(27)10477-10490(2024).