Correlation Engine 2.0
Clear Search sequence regions

  • cell (4)
  • cellular (1)
  • child (1)
  • female (1)
  • growth (1)
  • HDAC (2)
  • hdac inhibitor (1)
  • humans (1)
  • jnj 26481585 (3)
  • mice (1)
  • mice balb c (1)
  • mice nod (1)
  • mice scid (1)
  • pptp (3)
  • signals (1)
  • t cell (1)
  • vitro (3)
  • xenografts (8)
  • Sizes of these terms reflect their relevance to your search.

    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. Quisinostat was tested against the PPTP in vitro panel at concentrations ranging from 1.0 nM to 10 μM and was tested against the PPTP in vivo panels at a dose of 5 mg/kg (solid tumors) or 2.5 mg/kg (ALL models) administered intraperitoneally daily × 21. 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 2.2 nM (range <1-19 nM). quisinostat induced significant differences in EFS distribution compared to control in 21 of 33 (64%) of the evaluable solid tumor xenografts and in 4 of 8 (50%) of the evaluable ALL xenografts. An objective response was observed in 1 of 33 solid tumor xenografts while for the ALL panel, two xenografts achieved complete response (CR) or maintained CR, and a third ALL xenograft achieved stable disease. Quisinostat demonstrated broad activity in vitro, and retarded growth in the majority of solid tumor xenografts studied. The most consistent in vivo activity signals observed were for the glioblastoma xenografts and T-cell ALL xenografts. © 2013 Wiley Periodicals, Inc.


    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. Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program. Pediatric blood & cancer. 2014 Feb;61(2):245-52

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 24038993

    View Full Text