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.


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


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