Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

Ulrike Leurs; Rasmus P Clausen; Jesper L Kristensen; Brian Lohse

doi:10.1016/j.bmcl.2012.07.091

Inhibitor scaffold for the histone lysine demethylase KDM4C (JMJD2C)

Bioorg Med Chem Lett. 2012 Sep 15;22(18):5811-3. doi: 10.1016/j.bmcl.2012.07.091. Epub 2012 Aug 2.

Authors

Ulrike Leurs¹, Rasmus P Clausen, Jesper L Kristensen, Brian Lohse

Affiliation

¹ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.

PMID: 22917519
DOI: 10.1016/j.bmcl.2012.07.091

Abstract

The human histone demethylases of the KDM4 (JMJD2) family have been associated to diseases such as prostate and breast cancer, as well as X-linked mental retardation. Therefore, these enzymes are considered oncogenes and their selective inhibition might be a possible therapeutic approach to treat cancer. Here we describe a heterocyclic ring system library screened against the histone demethylase KDM4C (JMJD2C) in the search for novel inhibitory scaffolds. A 4-hydroxypyrazole scaffold was identified as an inhibitor of KDM4C; this scaffold could be employed in the further development of novel therapeutics, as well as for the elucidation of the biological roles of KDM4C on epigenetic regulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dose-Response Relationship, Drug
Drug Design*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Humans
Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors*
Jumonji Domain-Containing Histone Demethylases / metabolism
Molecular Structure
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Small Molecule Libraries / chemistry*
Small Molecule Libraries / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
KDM4C protein, human
Pyrazoles
Small Molecule Libraries
4-hydroxypyrazole
Jumonji Domain-Containing Histone Demethylases