AZD5582 acetate is an inhibitor of IAPs, which binds to the BIR3 domains cIAP1, cIAP2, and XIAP with IC50s of 15, 21, and 15 nM, respectively. AZD5582 induces apoptosis.

CIAP1:15 nM, XIAP:15 nM, CIAP2:21 nM

AZD5582 (20 nM; 48 hours) inhibited cell viability by cooperation with IFNγ or viral double-stranded RNA (dsRNA) in H1975 NSCLC cells[2]. AZD5582 (20 nM; 48 hours) involves in apoptosis due to induction of cell death and active caspase-3/ -8 activities by AZD5582 and IFNγ co-treatment in HCC827 NSCLC cells[2]. AZD5582 (20 nM; 17 or 25 hours) down-regulates cIAP-1, activates RIPK1( upstream regulator of caspase-8), and triggers the activation of extrinsic (caspase-8) and intrinsic (caspase-9) apoptosis pathways, causing the cleavage of caspase-3 and caspase-7[2].

AZD5582 (intravenous injection; 0.1-3.0 mg/kg; once a week; 2 weeks) causes degradation of cIAP1 and caspase 3 cleavage in tumor cells, and after a two-week treatment, the tumors largely resolved. When the mice are given a medium dose (0.5 mg/kg) of AZD5582, cIAP1 degrades after administration, but it takes a while time to reach apoptosis-inducing effect[1].