Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program

摘要

AT13387, a non-geldanamycin inhibitor of heat-shock protein 90 (HSP90), was tested against the PPTP in vitro panel (1.0nM to 10μM) and against the PPTP in vivo panels (40 or 60mg/kg) administered orally twice weekly. In vitro AT13387 showed a median EC 50 value of 41nM and exhibited activity consistent with a cytotoxic effect. In vivo AT13387 induced significant differences in EFS distribution compared to controls in 17% evaluable solid tumor xenografts, but in none of the ALL xenografts. No objective tumor responses were observed. In vivo AT13387 demonstrated only modest single agent activity.