Development of a Water-Soluble Indolylmaleimide Derivative IM-93 Showing Dual Inhibition of Ferroptosis and NETosis.

ABSTRACT: The indolylmaleimide (IM) derivative IM-17 shows inhibitory activity against oxidative-stress-induced necrotic cell death and cardioprotective activity in rat ischemia-reperfusion injury models. In order to develop a more potent derivative, we conducted a detailed structure-activity relationship study of IM derivatives and identified IM-93 as the most potent derivative with good water solubility. IM-93 inhibited ferroptosis and NETosis, but not necroptosis or pyroptosis. In contrast, ferrostatin-1 (Fer-1), a ferroptosis inhibitor, did not inhibit NETosis, although the accompanying lipid peroxidation was partially inhibited by Fer-1, as well as by IM-93. Thus, IM derivatives have a unique activity profile and appear to be promising candidates for in vivo a

SUBMITTER: Dodo K 

PROVIDER: S-EPMC6746101 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature