Navitoclax is a potent and orally bioavailable Bcl-2 family protein inhibitor that binds with high affinity (Ki < 1 nM) to multiple anti-apoptotic Bcl-2 family proteins including Bcl-xL, Bcl-2 and Bcl-w.
Navitoclax (ABT-263) is active against approximately one-half of the cell lines of the PPTP in vitro panel. The median IC50 for all of the lines in the panel is 1.91 µM[1]. Navitoclax in combination with chemotherapy agents leads most ovarian cancer cell lines a synergistic response, and enhances the caspase activation at all paclitaxel doses tested in both SK-OV-3 and IGROV-1 cell lines.Navitoclax (100 mg/kg/day, p.o.) also improves responses to bendamustine-rituximab (BR) in a subset of tumours in mice xenograft.
To measure caspase-3/7 activation, IGROV-1 and SKOV3 cells are seeded in 96-well plates at 5,000 cells per well. After 24 hours, cells are treated with navitoclax (1 μM), paclitaxel (dose range=1-100 nM), or in combination with navitoclax and paclitaxel using the same dosing concentrations. Each treatment is done in duplicate wells. Induction of apoptosis, following treatment at time 0, 4, 24, and 48 hours, is determined using a Caspase-Glo 3/7 assay. A DMSO control is included in all studies. The experiment is conducted twice, and the data are presented as an average of both runs.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
