GPX4-IN-3 (26a) is a potent glutathione peroxidase 4 (GPX4) inhibitor as a selective ferroptosis inducer. GPX4-IN-3 (26a) exhibits 71.7% inhibition for GPX4 with 1 μM[1].
GPX4-IN-3 (26a) exhibits IC50 values of 0.78 μM, 6.9 μM, 0.15 μM and 4.73 μM in 4T1, MCF-7, HT1080 and HT1080 (with Fer-1) cells, respectively[1].GPX4-IN-3 (26a) exhibits outstanding GPX4 inhibitory activity with a percent inhibition up to 71.7% at 1.0 μM compared to 45.9% of RSL-3[1].GPX4-IN-3 (26a) could significantly induce lipid peroxide (LPO) increase and effectively induce ferroptosis with satisfactory selectivity[1].GPX4-IN-3 (26a) is more likely to induce ferroptosis through the accumulation of intracellular peroxides via inhibiting GPX4 activity[1].GPX4-IN-3 (26a) significantly increased the level of ROS in 4T1 cells, which could also be reversed by Ferrostatin-1 (fer-1)[1].
GPX4-IN-3 (26a) exertes antitumor activity and good biological safety in vivo[1].
[1]. Congjun Xu, et al. Discovery of a Potent Glutathione Peroxidase 4 Inhibitor as a Selective Ferroptosis Inducer. J Med Chem. 2021 Sep 23;64(18):13312-13326.