Identification of KD5170: a novel mercaptoketone-based histone deacetylase inhibitor

  • Bioorg Med Chem Lett. 2008 Dec 1;18(23):6093-6. doi: 10.1016/j.bmcl.2008.10.029.
Joseph E Payne  1 ,  Céline Bonnefous ,  Christian A Hassig ,  Kent T Symons ,  Xin Guo ,  Phan-Manh Nguyen ,  Tami Annable ,  Paul L Wash ,  Timothy Z Hoffman ,  Tadimeti S Rao ,  Andrew K Shiau ,  James W Malecha ,  Stewart A Noble ,  Jeffrey H Hager ,  Nicholas D Smith
Affiliations
  • 1. Department of Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA.
PMID: 18954983 DOI: 10.1016/j.bmcl.2008.10.029
Abstract

We report the identification of KD5170, a potent mercaptoketone-based Class I and II-histone deacetylase inhibitor that demonstrates broad spectrum cytotoxic activity against a range of human tumor-derived cell lines. KD5170 exhibits robust and sustained histone H3 hyperacetylation in HCT-116 xenograft tumors following single oral or i.v. dose and inhibition of tumor growth following chronic dosing.