IAP antagonist Compound A is a highly potent, Smac-mimetic IAP antagonist with equivalent binding affinity to XIAP and cIAP1 in the picomolar range, induces rapid degradation of cIAP1, activates NF-κB signaling via inhibtion of cIAP1 and induces TNFα-dependent apoptosis.
IAP antagonist Compound A competes with Smac for binding to IAPs and also for caspase 9 binding and interacts specifically with the BIR2 and BIR3 domains of cIAP1, cIAP2, and XIAP.
IAP antagonist Compound A (5 nM and 500 nM) exhibits significant killing of Kym1, OVCAR4, and SKOV3 lines.
IAP antagonist Compound A induces rapid degradation of cIAP1 in a binding- and proteasomal-dependent manner.
IAP antagonist Compound A activates NF-κB signaling and induces production of TNFα in an NF-κB-dependent manner in drug-sensitive cell lines.
Brefeldin A and Geldanamycin could blocked cell death induced by compound A.
IAP antagonist Compound A sensitized cells to TNFα-induced cell death.