Navitoclax | HY-10087

Navitoclax (ABT-263) is a potent and orally active Bcl-2 family protein inhibitor that binds to multiple anti-apoptotic Bcl-2 family proteins, such as Bcl-x_L, Bcl-2 and Bcl-w, with a K_i of less than 1 nM

IC₅₀ & Target:

In Vitro:

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. Navitoclax in combination with chemotherapy agents leads most ovarian cancer cell lines a synergistic response, and enhances the caspase activation in both SK-OV-3 and IGROV-1 cell lines.

 In Vivo:

Navitoclax (100 mg/kg; orally; 21-day treatment) enhances the activity of OSI-744 in vivo. As a single agent, 100 mg/kg Navitoclax alone dosed daily has no significant antitumor activity, whereas daily dosing of OSI-744 at 50 mg/kg results in significant tumor stasis (%TGI=52) during a 21-day treatment period. Notably, the combination of Navitoclax and OSI-744 dosed daily for 21 consecutive days results in 98% TGI and durable tumor regressions in 100% of treated tumor-bearing mice.

Formula:

SMILES:

O=S(C1=CC(S(NC(C2=CC=C(N3CCN(CC4=C(CCC(C(C4)C)C5=CC=C(Cl)C=C5)CC3)C=C2)=O)(=O)=O)=CC=C1N[C@H](CCN6CCOCC6)CSC7=CC=CC=C7)(C(F)(F)F)=O

Storage: