Development of a chimeric c-Src kinase and HDAC inhibitor

  • ACS Med Chem Lett. 2013 Aug 8;4(8):779-783. doi: 10.1021/ml400175d.
Kristin S Ko  1 ,  Michael E Steffey ,  Kristoffer R Brandvold ,  Matthew B Soellner
Affiliations
  • 1. Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, Michigan 48109, United States.
PMID: 24015327 DOI: 10.1021/ml400175d
Abstract

On the basis of synergism observed between a selective c-Src kinase inhibitor with an HDAC Inhibitor, the development of the first chimeric c-Src kinase and HDAC Inhibitor is described. The optimized chimeric inhibitor is shown to be a potent c-Src and HDAC Inhibitor. Chimeric inhibitor 4 is further shown to be highly efficacious in Cancer cell lines and significantly more efficacious than a dual-targeting strategy using discrete c-Src and HDAC inhibitors.

Keywords
HDAC; c-Src; chimera; combination therapy; kinase.