Epigenetic targets and drug discovery Part 2: Histone demethylation and DNA methylation

Pharmacol Ther. 2015 Jul:151:121-40. doi: 10.1016/j.pharmthera.2015.04.001. Epub 2015 Apr 7.

Abstract

Chromatin structure is dynamically modulated by various chromatin modifications, such as histone/DNA methylation and demethylation. We have reviewed histone methyltransferases and methyllysine binders in terms of small molecule screening and drug discovery in the first part of this review series. In this part, we will summarize recent progress in chemical probe and drug discovery of histone demethylases and DNA methyltransferases. Histone demethylation and DNA methylation have attracted a lot of attention regarding their biology and disease implications. Correspondingly, many small molecule compounds have been designed to modulate the activity of histone demethylases and DNA methyltransferases, and some of them have been developed into therapeutic drugs or put into clinical trials.

Keywords: Chemical probe; DNA methylation; Drug discovery; Histone demethylation; Inhibitor.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • DNA Methylation
  • DNA Modification Methylases / antagonists & inhibitors
  • DNA Modification Methylases / metabolism*
  • Drug Discovery
  • Epigenesis, Genetic*
  • Histone Demethylases / antagonists & inhibitors
  • Histone Demethylases / chemistry
  • Histone Demethylases / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Models, Molecular
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Protein Conformation

Substances

  • Antineoplastic Agents
  • Histone Demethylases
  • Jumonji Domain-Containing Histone Demethylases
  • DNA Modification Methylases