Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin
- 作者：Shinichi Sato ; Masashi Tetsuhashi ; Keiko Sekine ; Hiroyuki Miyachi ; Mikihiko Naito ; Yuichi Hashimoto ; Hiroshi Aoyama
- 关键词：Bestatin ; Actinonin ; cIAP1 ; Structural development ; Inhibitor
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2008
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 April 2008
- 卷：16
- 期：8
- 页码：4685-4698
- 文件大小：952 K
摘要
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 
-position of the internal amide carbonyl group, and the presence of a small substituent at the -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 μM) among the compounds prepared.
-position of the internal amide carbonyl group, and the presence of a small substituent at the -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 μM) among the compounds prepared.