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

  • ACS Med Chem Lett. 2018 Jan 29;9(3):182-187. doi: 10.1021/acsmedchemlett.7b00454.
Kosuke Dodo  1  2  3  4 ,  Tadashi Shimizu  1  3 ,  Jun Sasamori  5 ,  Kazuyuki Aihara  5 ,  Naoki Terayama  1  4 ,  Shuhei Nakao  1  4 ,  Katsuya Iuchi  1  2 ,  Masahiro Takahashi  3 ,  Mikiko Sodeoka  1  2  4
Affiliations
  • 1. RIKEN, Synthetic Organic Chemistry Laboratory, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan.
  • 2. Sodeoka Live Cell Chemistry Project, ERATO, JST, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan.
  • 3. Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, 2-1-1, Katahira, Aoba, Sendai, Miyagi 980-8577, Japan.
  • 4. AMED-CREST, AMED, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
  • 5. Drug Research Department, Fukushima Research Laboratories, Toa Eiyo Ltd., 1,Yuno-tanaka, Iizaka-machi, Fukushima-shi, Fukushima 960-0280, Japan.
PMID: 29541357 DOI: 10.1021/acsmedchemlett.7b00454
Abstract

We previously developed IM-54 as a novel type of inhibitor of hydrogen-peroxide-induced necrotic cell death. Here, we examined its cell death inhibition profile. IM-54 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. IM-17, an IM derivative having improved water-solubility and metabolic stability, was developed and confirmed to retain necrosis-inhibitory activity. IM-17 showed cardioprotective effects in an isolated rat heart model and an in vivo arrhythmia model, suggesting that IM derivatives may have therapeutic potential.

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