Birinapant (TL32711) is a bivalent, selective small molecule SMAC mimetic, binds with high affinity to multiple members of the IAP family with Kd of 45 nM and <1 nM for XIAP and cIAP1 respectively.
Birinapant (TL32711) binds to the BIR3 domains of cIAP1, cIAP2, XIAP, and the BIR domain of ML-IAP in vitro.
v specifically targets cIAP1 and cIAP2 for degradation, resulting in a switch in TNFR signaling; activation of TNFR upon binding of TNF-α in the presence of cIAP1 and cIAP2 leads to NF-κB activation and increased cell proliferation.
Birinapant (TL32711) in combination with TNF-α elicites anti-melanoma effect in a parental and BRAF inhibitor resistant cell line.
Birinapant (TL32711) preferentially targets the TRAF2-associated cIAP1 and cIAP2 with subsequent inhibition of TNF-induced NF-κB activation.
Birinapant (TL32711) inhibits umor growth in multiple primary patient-derived xenotransplant models.