Small-molecule SMAC mimetics as new cancer therapeutics.

Small-molecule SMAC mimetics as new cancer therapeutics.
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DOI:
10.1016/j.pharmthera.2014.05.007
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发表时间:
2014-10
影响因子:
13.5
通讯作者:
Wang, Shaomeng
Wang, Shaomeng
中科院分区:
医学1区
文献类型:
--
作者:
Bai, Longchuan;Smith, David C.;Wang, Shaomeng

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细胞凋亡是一个受到严格调控的细胞过程,而对细胞凋亡的错误调控是人类癌症的一个标志。作为一种新的癌症治疗策略,靶向关键的凋亡调控因子以恢复肿瘤细胞的凋亡已成为一种新的治疗策略。XIAP、cIAP1和cIAP2是凋亡抑制蛋白(IAP)的成员,是细胞死亡和存活的关键调节因子,是新的癌症治疗的有吸引力的靶点。Smac/Diablo蛋白是XIAP、cIAP1和cIAP2的内源性拮抗剂。在过去的十年里,紧张的研究工作导致了几种小分子Smac模拟物的设计和开发,目前正在进行癌症治疗的临床试验。在本文中,我们将讨论XIAP、cIAP1和cIAP2在调节细胞死亡和存活中的作用,以及小分子Smac模拟物作为新的癌症治疗药物的设计和开发。
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.
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