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

Producción científica: Article › revisión exhaustiva

13 Citas (Scopus)

Resumen

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.

Idioma original	English (US)
Páginas (desde-hasta)	185-188
Número de páginas	4
Publicación	Pediatric Blood and Cancer
Volumen	59
N.º	1
DOI	https://doi.org/10.1002/pbc.23154
Estado	Published - jul 15 2012
Publicado de forma externa	Sí

ASJC Scopus subject areas

Hematology
Oncology
Pediatrics, Perinatology, and Child Health

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10.1002/pbc.23154

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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",

author = "Kang, \{Min H.\} and Reynolds, \{C. Patrick\} and Houghton, \{Peter J.\} and Denise Alexander and Morton, \{Christopher L.\} and Kolb, \{E. Anders\} and Richard Gorlick and Keir, \{Stephen T.\} and Hernan Carol and Richard Lock and Maris, \{John M.\} and Amy Wozniak and Smith, \{Malcolm A.\}",

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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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AB - 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.

KW - Developmental therapeutics

KW - Hsp90 inhibitors

KW - Preclinical testing

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AN - SCOPUS:84861203569

SN - 1545-5009

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JO - Pediatric Blood and Cancer

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

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ASJC Scopus subject areas

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