First-in-class pan caspase inhibitor developed for the treatment of liver disease

…, LS Chen, N Chen, B Ching, P Contreras…

文献索引：Linton, Steven D.; Aja, Teresa; Armstrong, Robert A.; Bai, Xu; Chen, Long-Shiuh; Chen, Ning; Ching, Brett; Contreras, Patricia; Diaz, Jose-Luis; Fisher, Craig D.; Fritz, Lawrence C.; Gladstone, Patricia; Groessl, Todd; Gu, Xin; Herrmann, Julia; Hirakawa, Brad P.; Hoglen, Niel C.; Jahangiri, Kathy G.; Kalish, Vincent J.; Karanewsky, Donald S.; Kodandapani, Lalitha; Krebs, Joseph; McQuiston, Jeff; Meduna, Steven P.; Nalley, Kip; Robinson, Edward D.; Sayers, Robert O.; Sebring, Kristen; Spada, Alfred P.; Ternansky, Robert J.; Tomaselli, Kevin J.; Ullman, Brett R.; Valentino, Karen L.; Weeks, Suzanne; Winn, David; Wu, Joe C.; Yeo, Pauline; Zhang, Cheng-Zhi Journal of Medicinal Chemistry, 2005 , vol. 48, # 22 p. 6779 - 6782

全文：HTML全文

被引用次数: 63

摘要

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 α-Fas-induced liver injury. IDN-6556 (1) was further profiled in additional in vivo models and pharmacokinetic studies. This first-in-class ...