Indolylmaleimide Derivative IM-17 Shows Cardioprotective Effects in Ischemia-Reperfusion Injury

We previously developed <b>IM-54</b> as a novel type of inhibitor of hydrogen-peroxide-induced necrotic cell death. Here, we examined its cell death inhibition profile. <b>IM-54</b> was found to selectively inhibit oxidative stress-induced necrosis, but it did not inhibit apoptosis induced by various anticancer drugs or Fas ligand, or necroptosis. <b>IM-17</b>, an IM derivative having improved water-solubility and metabolic stability, was developed and confirmed to retain necrosis-inhibitory activity. <b>IM-17</b> showed cardioprotective effects in an isolated rat heart model and an <i>in vivo</i> arrhythmia model, suggesting that IM derivatives may have therapeutic potential