Histone deacetylase 2: A potential therapeutic target for cancer and neurodegenerative disorders

Eur J Med Chem. 2021 Apr 15:216:113332. doi: 10.1016/j.ejmech.2021.113332. Epub 2021 Mar 1.

Abstract

Histone deacetylases (HDACs) have been implicated in a number of diseases including cancer, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders and inflammation. For the treatment of epigenetically altered diseases such as cancer, HDAC inhibitors have made a significant progress in terms of development of isoform selective inhibitiors. Isoform specific HDAC inhibitors have less adverse events and better safety profile. A HDAC isoform i.e., HDAC2 demonstrated significant role in the development of variety of diseases, mainly involved in the cancer and neurodegenerative disorders. Discovery and development of selective HDAC2 inhibitors have a great potential for the treatment of target diseases. In the present compilation, we have reviewed the role of HDAC2 in progression of cancer and neurodegenerative disorders, and information on the drug development opportunities for selective HDAC2 inhibition.

Keywords: Cancer; Epigenetic mutation; HDAC inhibitors; HDAC2; Histone deacetylases (HDACs); Neurodegenerative disorders.

Publication types

  • Review

MeSH terms

  • Cell Cycle Checkpoints / drug effects
  • Drug Design
  • Histone Deacetylase 2 / antagonists & inhibitors*
  • Histone Deacetylase 2 / metabolism
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / metabolism
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / pathology
  • Signal Transduction / drug effects
  • Structure-Activity Relationship

Substances

  • Histone Deacetylase Inhibitors
  • Isoenzymes
  • Histone Deacetylase 2