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

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 α-position of the internal amide carbonyl group, and the presence of a small substituent at the α-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.

A series of hybrid compounds of bestatin and actinonin, which promote degradation cIAP1, were designed and synthesized. HAB-5A showed the most potent activity (IC50 = 0.53 μM) among the compounds prepared.Figure optionsDownload as PowerPoint slide