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

doi:10.1002/pbc.23154

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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	185-188
Number of pages	4
Journal	Pediatric Blood and Cancer
Volume	59
Issue number	1
DOIs	https://doi.org/10.1002/pbc.23154
State	Published - Jul 15 2012
Externally published	Yes

Keywords

Developmental therapeutics
Hsp90 inhibitors
Preclinical testing

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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10.1002/pbc.23154

Cite this

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

abstract = "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.",

keywords = "Developmental therapeutics, Hsp90 inhibitors, Preclinical testing",

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AU - Kang, Min H.

AU - Reynolds, C. Patrick

AU - Houghton, Peter J.

AU - Alexander, Denise

AU - Morton, Christopher L.

AU - Kolb, E. Anders

AU - Gorlick, Richard

AU - Keir, Stephen T.

AU - Carol, Hernan

AU - Lock, Richard

AU - Maris, John M.

AU - Wozniak, Amy

AU - Smith, Malcolm A.

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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