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 journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)185-188
Number of pages4
JournalPediatric Blood and Cancer
Volume59
Issue number1
DOIs
StatePublished - Jul 15 2012

Fingerprint

HSP90 Heat-Shock Proteins
Pediatrics
Heterografts
Neoplasms
(2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone
In Vitro Techniques
N-propyl-4-phenyl-1,2,3,6-tetrahydropyridine

Keywords

  • Developmental therapeutics
  • Hsp90 inhibitors
  • Preclinical testing

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Kang, M. H., Reynolds, C. P., Houghton, P. J., Alexander, D., Morton, C. L., Kolb, E. A., ... Smith, M. A. (2012). Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program. Pediatric Blood and Cancer, 59(1), 185-188. https://doi.org/10.1002/pbc.23154

Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program. / Kang, Min H.; Reynolds, C. Patrick; Houghton, Peter J.; Alexander, Denise; Morton, Christopher L.; Kolb, E. Anders; Gorlick, Richard; Keir, Stephen T.; Carol, Hernan; Lock, Richard; Maris, John M.; Wozniak, Amy; Smith, Malcolm A.

In: Pediatric Blood and Cancer, Vol. 59, No. 1, 15.07.2012, p. 185-188.

Research output: Contribution to journalArticle

Kang, MH, Reynolds, CP, Houghton, PJ, Alexander, D, Morton, CL, Kolb, EA, Gorlick, R, Keir, ST, Carol, H, Lock, R, Maris, JM, Wozniak, A & Smith, MA 2012, 'Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program', Pediatric Blood and Cancer, vol. 59, no. 1, pp. 185-188. https://doi.org/10.1002/pbc.23154
Kang, Min H. ; Reynolds, C. Patrick ; Houghton, Peter J. ; Alexander, Denise ; Morton, Christopher L. ; Kolb, E. Anders ; Gorlick, Richard ; Keir, Stephen T. ; Carol, Hernan ; Lock, Richard ; Maris, John M. ; Wozniak, Amy ; Smith, Malcolm A. / Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program. In: Pediatric Blood and Cancer. 2012 ; Vol. 59, No. 1. pp. 185-188.
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