JOURNAL ARTICLE

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

Min H Kang, C Patrick Reynolds, Peter J Houghton, Denise Alexander, Christopher L Morton, E Anders Kolb, Richard Gorlick, Stephen T Keir, Hernan Carol, Richard Lock, John M Maris, Amy Wozniak, Malcolm A Smith
Pediatric Blood & Cancer 2012 July 15, 59 (1): 185-8
21538821
AT13387, a non-geldanamycin inhibitor of heat-shock protein 90 (HSP90), was tested against the PPTP in vitro panel (1.0 nM to 10 µM) and against the PPTP in vivo panels (40 or 60 mg/kg) administered orally twice weekly. In vitro AT13387 showed a median EC(50) 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.

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