tcsc1719 Birinapant

Birinapant a bivalent Smac mimetic, is a potent antagonist for XIAP and cIAP1 with K_d values of 45 nM and < 1 nM, respectively.

IC50 & Target: Kd: 45 nM (XIAP), <1 nM (cIAP1)

In Vitro: Birinapant causes significant degradation of cIAP1 and 2. Birinapant + TRAIL-treated cells show increased levels of active caspase-8 and caspase-3, as well as PARP cleavage, over single agents within 4 h of treatment, indicative of apoptosis-mediated cell death. Birinapan significantly decreases the viability of SUM190 cells in a dose-dependent manner. Birinapant treatment in the XIAP knockdown cell line (SUM190 shXIAP) causes an overall reduction in viability at lower doses (30-300 nM)^[1]. Birinapant causes apoptosis in the sensitive cells. Birinapant in conbination with TNF-α, causes PARP cleavage in 451Lu and WM1366 cell lines^[2]. Birinapant induces time-course of caspase-3 activation in HCT116 human colon carcinoma and MDA-MB-231 human breast adenocarcinoma cells^[3].

In Vivo: Birinapant can inhibit tumor growth in melanoma xenotransplantation models. Staining for activated caspase-3 in biopsies of the same tumors show a modest increase in apoptotic cells in the birinapant treated animals^[2]. Birinapant (15 mg/kg, i.p.) induces apoptosis in HCT116 tumor-bearing mouse^[3].