IM-93 is a dual inhibitor of ferroptosis and NETosis.1 It inhibits tert-butyl hydroperoxide- and erastin-induced ferroptosis in NIH3T3 cells (IC50s =1.8 and 1.9 nM, respectively), as well as decreases NETosis induced by phorbol 12-myristate 13-acetate in isolated human peripheral blood neutrophils when used at concentrations ranging from 1.6 to 25 μM. IM-93 also inhibits hydrogen peroxide-induced necrosis in HL-60 cells (IC50 = 0.45 μM), but has no effect on necroptosis induced by Fas ligand in combination with Z-VAD-FMK and cycloheximide in Jurkat cells or pyroptosis induced by S. aureus and P. aeruginosa in THP-1 cells when used at a concentration of 25 μM.
|1. Dodo, K., Kuboki, E., Shimizu, T., et al. Development of a water-soluble indolylmaleimide derivative IM-93 showing dual inhibition of ferroptosis and NETosis. ACS Med. Chem. Lett. 10(9), 1272-1278 (2019).