Structure-based design, synthesis, and evaluation of conformationally constrained mimetics of the second mitochondria-derived activator of caspase that target the X-linked inhibitor of apoptosis protein/caspase-9 interaction site
Structure-based design, synthesis, and evaluation of conformationally constrained mimetics of the second mitochondria-derived activator of caspase that target the X-linked inhibitor of apoptosis protein/caspase-9 interaction site
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DOI：
10.1021/jm0499108
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发表时间：
2004-08-12
影响因子：
7.3
通讯作者：
Wang, SM
中科院分区：
文献类型：
--
作者：
Sun, HY;Nikolovska-Coleska, Z;Wang, SM
本文描述了一种基于构象约束的第二线粒体衍生caspase激活物（Smac）模拟物的成功结构设计，该模拟物靶向XIAP/caspase-9相互作用位点。最有效的Smac模拟12d与XIAP BIR3结构域蛋白结合的K-i为350 nM。12d对顺铂诱导的PC-3人前列腺癌细胞凋亡有增强作用。
A successful structure-based design of conformationally constrained second mitochondria-derived activator of caspase (Smac) mimetics that target the XIAP/caspase-9 interaction site is described. The most potent Smac mimetic 12d has a K-i of 350 nM for binding to the XIAP BIR3 domain protein. 12d is found to be effective in enhancing apoptosis induced by cisplatin in PC-3 human prostate cancer cells.