| Literature DB >> 16250635 |
Steven D Linton1, Teresa Aja, Robert A Armstrong, Xu Bai, Long-Shiuh Chen, Ning Chen, Brett Ching, Patricia Contreras, Jose-Luis Diaz, Craig D Fisher, Lawrence C Fritz, Patricia Gladstone, Todd Groessl, Xin Gu, Julia Herrmann, Brad P Hirakawa, Niel C Hoglen, Kathy G Jahangiri, Vincent J Kalish, Donald S Karanewsky, Lalitha Kodandapani, Joseph Krebs, Jeff McQuiston, Steven P Meduna, Kip Nalley, Edward D Robinson, Robert O Sayers, Kristen Sebring, Alfred P Spada, Robert J Ternansky, Kevin J Tomaselli, Brett R Ullman, Karen L Valentino, Suzanne Weeks, David Winn, Joe C Wu, Pauline Yeo, Cheng-zhi Zhang.
Abstract
A series of oxamyl dipeptides were optimized for pan caspase inhibition, anti-apoptotic cellular activity and in vivo efficacy. This structure-activity relationship study focused on the P4 oxamides and warhead moieties. Primarily on the basis of in vitro data, inhibitors were selected for study in a murine model of alpha-Fas-induced liver injury. IDN-6556 (1) was further profiled in additional in vivo models and pharmacokinetic studies. This first-in-class caspase inhibitor is now the subject of two Phase II clinical trials, evaluating its safety and efficacy for use in liver disease.Entities:
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Year: 2005 PMID： 16250635 DOI： 10.1021/jm050307e
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446