Birinapant is a bivalent mimetic of the Diablo homolog known as second mitochondria-derived activator of caspase (Smac). It is an antagonist of cellular inhibitor of apoptosis 1 (cIAP1, or BIRC2), cIAP2 (BIRC3), and XIAP (BIRC4), binding each at nanomolar concentrations. Birinapant causes rapid cIAP1 degradation, caspase activation, PARP cleavage, and NF-κB activation in breast cancer cells. It shows in vivo antitumor activity, inducing apoptosis in several types of cancer xenografts in mice.
Birinapant is a bivalent SMAC mimetic compound antagonist of TRAF2 associated cIAP1 and cIAP2.
ChEBI: Birinapant is a dipeptide.
This rotationally symmetric SMAC mimetic antagonist and anticancer agent (FW = 806.94 g/mol; CAS 1260251-31-7) targets cellular Inhibitor of Apoptosis Protein (or cIAP1; Kd of <1 nM), arguably the most potent mammalian caspase inhibitor, showing single-agent efficacy due to its panIAP antagonism and causing rapid cIAP1 degradation, caspase activation, PARP cleavage, and NF-κB activation. When administered in combination with TNF-α, Birinapant is effective against a melanoma cell line with acquired resistance to BRAF inhibitors
