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. (C) 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 10: 308-314; 2010: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.201000031