Description
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.
Uses
Birinapant is a bivalent SMAC mimetic compound antagonist of TRAF2 associated cIAP1 and cIAP2.
Definition
ChEBI: Birinapant is a dipeptide.
Enzyme inhibitor
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
References
[1] JENNIFER L ALLENSWORTH. Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism.[J]. Breast Cancer Research and Treatment, 2013, 137 2: 359-371. DOI:
10.1007/s10549-012-2352-6[2] CLEMENS KREPLER. The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells.[J]. Clinical Cancer Research, 2013, 19 7: 1784-1794. DOI:
10.1158/1078-0432.ccr-12-2518[3] QUANG-Dé NGUYEN. Temporal and spatial evolution of therapy-induced tumor apoptosis detected by caspase-3-selective molecular imaging.[J]. Clinical Cancer Research, 2013, 19 14: 3914-3924. DOI:
10.1158/1078-0432.ccr-12-3814
