Design, synthesis, and evaluation of a potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase (Smac) mimetic

被引：96

作者：

Sun, Haiying

Nikolovska-Coleska, Zaneta

Lu, Jianfeng

Qiu, Su

Yang, Chao-Yie

Gao, Wei

Meagher, Jennifer

Stuckey, Jeanne

Wang, Shaomeng

机构：

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

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

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

[4] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 26期

关键词：

D O I：

10.1021/jm061108d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase mimetic (SM-131, 2) has been designed, synthesized, and evaluated. Compound 2 binds to X-linked inhibitors of apoptosis proteins (XIAP) with a K-i of 61 nM in a competitive binding assay and directly antagonizes the XIAP inhibition of caspase-9 activity in a cell-free functional assay. Compound 2 achieves an IC50 of 100 nM in inhibition of cell growth and effectively induces cell death in the MDA-MB-231 human breast cancer cell line.

引用

收藏

页码：7916 / 7920

页数：5

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