Birinapant

1260251-31-7

C42H56F2N8O6

DMSO : >= 40 mg/mL (49.57 mM); H2O : < 0.1 mg/mL (insoluble)

Apoptosis; Apoptosis

Birinapant (TL32711), a bivalent Smac mimetic, is a potent antagonist for XIAP and cIAP1 with K_ds of 45 nM and less than 1 nM, respectively. Birinapant (TL32711) binds to the BIR3 domains of cIAP1, cIAP2, XIAP, and the BIR domain of ML-IAP in vitro and induces the autoubiquitylation and proteasomal degradation of cIAP1 and cIAP2 in intact cells, which results in formation of a RIPK1: caspase-8 complex, caspase-8 activation, and induction of tumor cell death. Birinapant (TL32711) preferentially targets the TRAF2-associated cIAP1 and cIAP2 with subsequent inhibition of TNF-induced NF-kappaB activation^[1][2]. IC50 & Target: Kd: 45 nM (XIAP), <1 nM (cIAP1)^[1] In Vitro: Birinapant (TL32711) (30-10000 nM; 24 hours) significantly decreases the viability of SUM190 cells in a dose-dependent manner^[1].
Birinapant (TL32711) (30-1000 nM; 4 hours) shows a significant decrease in cIAP1 levels and enhanced PARP cleavage, and induces apoptosis^[1]. 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^[2].