Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin
Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin
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DOI：
10.1016/j.bmc.2008.02.024
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发表时间：
2008-04-15
影响因子：
3.5
通讯作者：
Aoyama, Hiroshi
中科院分区：
文献类型：
--
作者：
Sato, Shinichi;Tetsuhashi, Masashi;Aoyama, Hiroshi
设计并合成了一系列促进细胞凋亡抑制蛋白1（cIAP 1）降解的bestatin（1）和actinonin（3）杂合化合物。结构-活性关系研究表明，绝对构型、内部酰胺羰基α位的疏水性以及酯基α位存在小取代基是表达有效cIAP 1降解促进活性的重要因素。HAB-5A（30 b）在所制备的化合物中显示最有效的活性（IC 50 = 0.53 μ M）。(c)2008爱思唯尔有限公司保留所有权利。
A series of hybrid compounds of bestatin ( 1) and actinonin ( 3), which promote degradation of cellular inhibitor of apoptosis protein 1 (cIAP1), were designed and synthesized. Structure-activity relationship studies indicated that absolute configuration, hydrophobicity at the alpha-position of the internal amide carbonyl group, and the presence of a small substituent at the alpha-position of the ester group are important factors for the expression of potent cIAP1 degradation-promoting activity. HAB-5A (30b) showed the most potent activity (IC50 = 0.53 mu M) among the compounds prepared. (c) 2008 Elsevier Ltd. All rights reserved.