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

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.

• Authors: Joseph E Payne, 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
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 23 Pg. 6093-6 (Dec 01 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18954983 (Publication Type: Journal Article)

Chemical References

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

Topics

• Animals
• Antineoplastic Agents (chemistry, 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, pharmacology)
• Pyridines (chemistry, pharmacology)
• Structure-Activity Relationship
• Sulfonamides (chemistry, pharmacology)
• Xenograft Model Antitumor Assays