Dimeric Smac mimetic; potent inhibitor of X-linked (XIAP) and cellular (cIAP) inhibitor of apoptosis protein (IC50
values are 15, 15 and 21 nM for XIAP, cIAP1 and cIAP2 respectively). Binds to the BIR3 domain of XIAP to prevent interaction with caspase-9. Causes degradation of cIAP1 and cIAP2 and induces apoptosis in MDA-MB-231 breast cancer cells. Causes tumor regression in MDA-MB-231 xenograft-bearing mice.
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Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582).
Hennessy et al.