Daniel Romo,Jun Liu,Nam Song Choi,Zonggao Shi,Woon-Kai Low,Yongjun Dang,Tilman Schneider-Poetsch
申请号：
US12813858
公开号：
US08841285B2
申请日:
2010.06.11
申请国别(地区):
US
年份:
2014
代理人:
摘要：
Provided herein include compositions, all related stereoisomers as well as pharmaceutically acceptable salts provided as simplified analogs of pateamine A, in which the analogs generally are devoid of the C3-amino and C5-methyl groups, also referred to as desmethyl, desamino-pateamine A. Suitable analogs provide anticancer and antiproliferative effects in vivo and in vitro by a novel drugs mechanism of action described herein for pateamine A, including inhibition of eIF4A-dependent translation initiation. As with pateamine A, as described herein, suitable analogs cause cell cycle arrest or induce apoptosis in transformed cells. However, toxicity of such compounds to slow growing normal cells is low. In addition, such analogs, like pateamine A, target translation initiation factors and are useful as anticancer and antiproliferative agents in subjects in need thereof. Moreover, the analogs, like pateamine A, are valuable molecular probes for evaluation of eukaryotic translation initiation and as lead compounds for development of improved anticancer agents.
