AZD5582

Biochem/physiol Actions

AZD5582 is a divalent AVPI motif-based Smac (DIABLO) mimetic (SMC) that acts a potent apoptosis protein repeat (BIR) domain-targeting antagonist against inhibitor of apoptosis proteins (IAPs) cIAP1/2 (BIR3 IC₅₀ = 15/21 nM against 2.5 nM AbuRPFK-5FAM) and XIAP (BIR2/3 IC₅₀ = 21/15 nM). AZD5582 abolishes cellular XIAP-caspase-9 interaction (1 µM, 4 hrs), induces cIAP1/2 degradation (EC₅₀ = 0.1 nM, 1 hr) and apoptosis (GI₅₀ ﹤60 pM, 48 hrs) in MDA-MB-231 breast cancer cultures. AZD5582 causes substantial tumor regression by inducing cIAP1 degradation and apoptosis in tumor cells in MDA-MB-231 xenograft-bearing mice in vivo (3.0 mg/kg/wk i.v.).