A small molecule Smac mimic potentiates TRAIL- and TNFα-mediated cell death

被引：570

作者：

Li, L

Thomas, RM

Suzuki, H

De Brabander, JK

Wang, XD

Harran, PG

机构：

[1] Univ Texas, SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

[2] Univ Texas, SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

SCIENCE | 2004年 / 305卷 / 5689期

关键词：

D O I：

10.1126/science.1098231

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We describe the synthesis and properties of a small molecule mimic of Smac, a pro-apoptotic protein that functions by relieving inhibitor-of-apoptosis protein (IAP)-mediated suppression of caspase activity. The compound binds to X chromosome-encoded IAP (XIAP), cellular IAP 1 (clAP-1), and cellular IAP 2 (clAP-2) and synergizes with both tumor necrosis factor alpha (TNFalpha.) and TNF-related apoptosis-inducing ligand (TRAIL) to potently induce caspase activation and apoptosis in human cancer cells. The molecule has allowed a temporal, unbiased evaluation of the roles that IAP proteins play during signaling from TRAIL and TNF receptors. The compound is also a lead structure for the development of IAP antagonists potentially useful as therapy for cancer and inflammatory diseases.

引用

页码：1471 / 1474

页数：4

共 25 条

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