Birinapant

Birinapant (also known as TL32711) is a SMAC mimetic antagonist and an inhibitor of IAP (Inhibitor of Apoptosis Protein) family proteins, with antitumor activity in vivo. Birinapant has high binding affinity (nM range) for cIAP1/2 and XIAP. Birinapant (TL32711) caused rapid cIAP1 degradation, caspase activation, PARP cleavage, and NF-κB activation. Birinapant induces cell death as a single agent in TRAIL-insensitive SUM190 (ErbB2-overexpressing) cells and significantly increases potency of TRAIL-induced apoptosis in TRAIL-sensitive SUM149 (triple-negative, EGFR-activated) cells. TL32711 (Birinapant) combined with TNF-α inhibited the growth of a melanoma cell line with acquired resistance to BRAF inhibition to the same extent as in the parental cell line. In addition, Birinapant in combination or as a single agent decreased colony formation and anchorage-independent growth potential of IBC cells. TL32711 is currently in a phase 2 single agent and combination clinical studies in solid tumors.