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

AT13387, a non-geldanamycin inhibitor of heat-shock protein 90 (HSP90), was tested against the PPTP in vitro panel (1.0?nM to 10 mu M) and against the PPTP in vivo panels (40 or 60?mg/kg) administered orally twice weekly. In vitro AT13387 showed a median EC50 value of 41?nM 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. Pediatr Blood Cancer 2012; 59: 185188. (C) 2011 Wiley Periodicals, Inc.