Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program

Hernan Carol, Richard Gorlick, E. Anders Kolb, Christopher L. Morton, Donya Moradi Manesh, Stephen T. Keir, C. Patrick Reynolds, Min H. Kang, John M. Maris, Amy Wozniak, Ian Hickson, Dmitry Lyalin, Raushan T. Kurmasheva, Peter J. Houghton, Malcolm A. Smith, Richard Lock

Research output: Contribution to journalArticle

Abstract

Background: Quisinostat (JNJ-26481585) is a second-generation pyrimidyl-hydroxamic acid histone deacetylase (HDAC) inhibitor with high cellular potency towards Class I and II HDACs. Quisinostat was selected for clinical development as it showed prolonged pharmacodynamic effects in vivo and demonstrated improved single agent antitumoral efficacy compared to other analogs. Procedures: Quisinostat was tested against the PPTP in vitro panel at concentrations ranging from 1.0nM to 10μM and was tested against the PPTP in vivo panels at a dose of 5mg/kg (solid tumors) or 2.5mg/kg (ALL models) administered intraperitoneally daily×21. Results: In vitro quisinostat demonstrated potent cytotoxic activity, with T/C% values approaching 0% for all of the cell lines at the highest concentration tested. The median relative IC50 value for the PPTP cell lines was 2.2nM (range

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalPediatric Blood and Cancer
Volume61
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

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Keywords

  • Developmental therapeutics
  • HDAC inhibitor
  • Preclinical testing

ASJC Scopus subject areas

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

Cite this

Carol, H., Gorlick, R., Kolb, E. A., Morton, C. L., Manesh, D. M., Keir, S. T., Reynolds, C. P., Kang, M. H., Maris, J. M., Wozniak, A., Hickson, I., Lyalin, D., Kurmasheva, R. T., Houghton, P. J., Smith, M. A., & Lock, R. (2014). Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program. Pediatric Blood and Cancer, 61(2), 245-252. https://doi.org/10.1002/pbc.24724