Birinapant

Birinapant is a SMAC mimetic antagonist, mostly to cIAP1 with Kd of <1 nM, less potent to XIAP. Phase 2. (In Vitro) :Birinapant (TL32711) (30-10000 nM; 24 hours) significantly decreases the viability of SUM190 cells in a dose-dependent manner.Birinapant (TL32711) (30-1000 nM; 4 hours) shows a significant decrease in cIAP1 levels and enhanced PARP cleavage, and induces apoptosis.Birinapant (TL32711) binds with high affinity to the isolated BIR3 domains of cIAP1, cIAP2, and XIAP and the single BIR domain of ML-IAP and rapidly degrades TRAF2-bound cIAP1 and cIAP2 thereby inhibiting TNF-mediated NF-κB activation. (In Vivo) :Birinapant (TL32711) (30 mg/kg; i.p.; every third day (*5) ) shows antitumor efficacy and are devoid of overt toxicity in preclinical models.