Small-molecule SMAC mimetics as new cancer therapeutics

被引：169

作者：

Bai, Longchuan

Smith, David C.

Wang, Shaomeng

机构：

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

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

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

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

来源：

PHARMACOLOGY & THERAPEUTICS | 2014年 / 144卷 / 01期

关键词：

SMAC mimetics; Apoptosis; Inhibitors; NF-KAPPA-B; X-LINKED INHIBITOR; TRAIL-INDUCED APOPTOSIS; MIXED LINEAGE KINASE; CELL-DEATH COMPLEX; C-RAF KINASE; STRUCTURAL BASIS; IAP PROTEINS; ANTAGONISTS INDUCE; PROMOTES APOPTOSIS;

D O I：

10.1016/j.pharmthera.2014.05.007

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Apoptosis is a tightly regulated cellular process and faulty regulation of apoptosis is a hallmark of human cancers. Targeting key apoptosis regulators with the goal to restore apoptosis in tumor cells has been pursued as a new cancer therapeutic strategy. XIAP, cIAP1, and cIAP2, members of inhibitor of apoptosis (IAP) proteins, are critical regulators of cell death and survival and are attractive targets for new cancer therapy. The SMAC/DIABLO protein is an endogenous antagonist of XIAP, cIAP1, and cIAP2. In the last decade, intense research efforts have resulted in the design and development of several small-molecule SMAC mimetics now in clinical trials for cancer treatment. In this review, we will discuss the roles of XIAP, cIAP1, and cIAP2 in regulation of cell death and survival, and the design and development of small-molecule SMAC mimetics as novel cancer treatments. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：82 / 95

页数：14

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