Development of selective inhibitors of necrosis.
Oxidative stress-induced necrosis plays an important role in ischemia-reperfusion injury, such as stroke and heart attack. Here, we describe the development of selective inhibitors of necrosis, MS-1 and IM-54, as potential cardioprotective agents and biological tools for investigating the molecular mechanisms of cell death. By means of chemical modifications of kinase inhibitor BM I, its affinity for various kinases was successfully removed and a potent and selective inhibitor of necrosis, IM-54, was obtained. IM-54 inhibits necrosis induced by oxidative stress, but not apoptosis induced by anticancer drugs.
Sodeoka
Mikiko
M
RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. sodeoka@riken.jp
Dodo
Kosuke
K
D002316:Cardiotonic Agents / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000627:therapeutic use; D008301:Maleimides / Q000737:chemistry* / Q000627:therapeutic use; D009336:Necrosis / Q000378:metabolism*; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D011758:Pyrroles / Q000737:chemistry; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology
C527045:2-(1-(3-aminopropyl)indol-3-yl)-3-(indol-3-yl)-N-methylmaleimide; C503757:2-(1H-indol-3-yl)-3-pentylamino-maleimide; D002316:Cardiotonic Agents; D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D011493:Protein Kinase C