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. Epub 2008 Oct 11.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / pharmacology*
  • HCT116 Cells
  • Histone Deacetylase Inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • KD 5170
  • Prodrugs
  • Pyridines
  • Sulfonamides