Small molecule KDM4s inhibitors as anti-cancer agents

J Enzyme Inhib Med Chem. 2018 Dec;33(1):777-793. doi: 10.1080/14756366.2018.1455676.

Abstract

Histone demethylation is a vital process in epigenetic regulation of gene expression. A number of histone demethylases are present to control the methylated states of histone. Among these enzymes, KDM4s are one subfamily of JmjC KDMs and play important roles in both normal and cancer cells. The discovery of KDM4s inhibitors is a potential therapeutic strategy against different diseases including cancer. Here, we summarize the development of KDM4s inhibitors and some related pharmaceutical information to provide an update of recent progress in KDM4s inhibitors.

Keywords: Cancer; KDM4s inhibitors; epigenetic; histone demethylation.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors*
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Mice
  • Molecular Structure
  • RAW 264.7 Cells
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Small Molecule Libraries
  • Tumor Necrosis Factor-alpha
  • Jumonji Domain-Containing Histone Demethylases
  • KDM4A protein, human

Grants and funding

This work was supported by the National Natural Science Foundation of China under Grants [81402851 and 81573281]; Natural Science Foundation of Jiangsu Province under Grant [BK20140957]; and Fundamental Research Funds for the Central Universities under Grant [2015ZD009], Jiangsu Qing Lan Project.