Structure-based design of potent, conformationally constrained Smac mimetics

被引：134

作者：

Sun, HY

Nikolovska-Coleska, Z

Yang, CY

Xu, L

Liu, ML

Tomita, Y

Pan, HG

Yoshioka, 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] Natl Canc Inst Frederick, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2004年 / 126卷 / 51期

关键词：

D O I：

10.1021/ja047438+

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A successful structure-based design and synthesis of a class of highly potent conformationally constrained Smac mimetics is described. The most potent compound has a Ki value of 25 nM binding to the XIAP BIR3 protein and is 23 times more potent than natural Smac peptides. These potent Smac mimetics can serve as powerful chemical and pharmacological tools to further elucidate the role of Smac and its cellular binding partners in apoptosis regulation and may be developed as a new class of anti-cancer drugs. Copyright © 2004 American Chemical Society.

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页码：16686 / 16687

页数：2

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