A-385358, is a selective inhibitor of Bcl-XL with Kis, in vitro. In vivo, A-385358, in combination with the lower dose of paclitaxel produces a significant reduction in tumor growth (%T/C) compare with paclitaxel monotherapy.
in vivo
The combination of A-385358 given at 100 mg/kg/d plus the lower dose of paclitaxel produces a significant reduction in tumor growth (%T/C) compare with paclitaxel monotherapy. This combination also yields a >100% increase in time for tumors to reach 900 mm3 (%ILS) compare with vehicle control. Maximal efficacy is observed during the dosing period for A-385358, with slow but steady increase in the tumor growth after termination of treatment. The combination of A-385358 at 75 mg/kg/d plus paclitaxel at 30 mg/kg/d is also well tolerated and inhibits tumor growth rate by nearly 80%. Significant effects on tumor growth relative to paclitaxel monotherapy are observed with doses as low as 50 mg/kg/d[1].