Alpha-mercaptoketone based histone deacetylase inhibitors

  • Bioorg Med Chem Lett. 2008 Dec 15;18(24):6482-5. doi: 10.1016/j.bmcl.2008.10.058.
Paul L Wash  1 ,  Timothy Z Hoffman ,  Brandon M Wiley ,  Céline Bonnefous ,  Nicholas D Smith ,  Michael S Sertic ,  Charles M Lawrence ,  Kent T Symons ,  Phan-Manh Nguyen ,  Kevin D Lustig ,  Xin Guo ,  Tami Annable ,  Stewart A Noble ,  Jeffrey H Hager ,  Christian A Hassig ,  James W Malecha
Affiliations
  • 1. Department of Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA.
PMID: 18954984 DOI: 10.1016/j.bmcl.2008.10.058
Abstract

In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.