Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin

作者：Sato Shinichi; Tetsuhashi Masashi; Sekine Keiko; Miyachi Hiroyuki; Naito Mikihiko; Hashimoto Yuichi; Aoyama Hiroshi^*

来源：Bioorganic & Medicinal Chemistry, 2008, 16(8): 4685-4698.

DOI：10.1016/j.bmc.2008.02.024

• bestatin
• actinonin
• cIAP1
• structural development
• inhibitor

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.

• 出版日期2008-4-15