Lack of in vivo bioactivity of GX015-070. (A) Mice were randomly assigned (8-10/group) to receive vehicle (□) 4 mg/kg GX015-070 (♦) by intravenous injection for 10 of 14 days (indicated by solid line) on day 11 when tumors were palpable. Results are tumor volume (mean ± SD mm3) plotted against time. (B) At the completion of treatment, mice from vehicle-treated (−) or GX015-070–treated (GX; +) group were killed, and the tumors were removed and analyzed for pharmacodynamic activity. KMS12-PE tumors were immediately homogenized in ice-cold lysis buffer and Bak was immunoprecipitated from 1 mg protein with anti-Bak and immunoblotting with anti–Mcl-1 was performed (upper panel). Then blot was stripped and probed with an anti-Bak as a loading control (lower panel). GX015-070 failed to inhibit the in vivo Mcl-1/Bak interaction in mice tumors.
