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

被引：119

作者：

Sun, HY

Nikolovska-Coleska, Z

Yang, CY

Xu, L

Tomita, Y

Krajewski, K

Roller, PP

Wang, SM

机构：

[1] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[4] Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA

[5] NCI, FCRDC, Med Chem Lab, Frederick, MD 21702 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 17期

关键词：

D O I：

10.1021/jm0499108

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

收藏

页码：4147 / 4150

页数：4

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