Emerging approaches for histone deacetylase inhibitor drug discovery

Expert Opin Drug Discov. 2015 Jun;10(6):599-613. doi: 10.1517/17460441.2015.1038236. Epub 2015 Apr 20.

Abstract

Introduction: Histone deacetylases (HDACs) are key players in the mediation of gene expression for both cancerous and noncancerous malignancies. Overexpression of these enzymes has been demonstrated in numerous types of cancer with some enzyme isoforms also involved in neurological, inflammatory and viral pathologies. Hence, the development of HDAC inhibitors (HDACis) represents a promising approach for their treatment. Numerous chemical entities have been studied in the recent years and some of them have reached clinical trials.

Areas covered: This review summarizes the recent efforts in the drug development of HDACis and their potential application as therapeutic agents in cancerous, neurological, inflammatory and viral diseases.

Expert opinion: The development of novel potent and selective HDACis is ongoing. However, increased scientific effort is needed to aid the fight of specific types of cancerous or noncancerous disease with more selective agents required to avoid side effects during therapy. An interesting therapeutic approach is the use of HDACis in combination with other epigenetic target modulators to combine their therapeutic potential for a synergistic effect.

Keywords: cancer; epigenetics; histone deacetylases; inhibitors; neurology; small molecules; viral infections.

Publication types

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

MeSH terms

  • Animals
  • Drug Design
  • Drug Discovery / methods*
  • Drug Synergism
  • Drug Therapy, Combination
  • Gene Expression Regulation
  • Histone Deacetylase Inhibitors / administration & dosage
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / drug effects*
  • Histone Deacetylases / genetics
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / enzymology

Substances

  • Histone Deacetylase Inhibitors
  • Histone Deacetylases