HDAC8: a multifaceted target for therapeutic interventions

Trends Pharmacol Sci. 2015 Jul;36(7):481-92. doi: 10.1016/j.tips.2015.04.013. Epub 2015 May 23.


Histone deacetylase 8 (HDAC8) is a class I histone deacetylase implicated as a therapeutic target in various diseases, including cancer, X-linked intellectual disability, and parasitic infections. It is a structurally well-characterized enzyme that also deacetylates nonhistone proteins. In cancer, HDAC8 is a major 'epigenetic player' that is linked to deregulated expression or interaction with transcription factors critical to tumorigenesis. In the parasite Schistosoma mansoni and in viral infections, HDAC8 is a novel target to subdue infection. The current challenge remains in the development of potent selective inhibitors that would specifically target HDAC8 with fewer adverse effects compared with pan-HDAC inhibitors. Here, we review HDAC8 as a drug target and discuss inhibitors with respect to their structural features and therapeutic interventions.

Keywords: Cornelia de Lange syndrome; HDAC8; X-ray crystallography; cancer; histone deacetylases; schistosoma.

Publication types

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

MeSH terms

  • Animals
  • De Lange Syndrome / drug therapy
  • De Lange Syndrome / enzymology
  • Enzyme Activators / chemistry
  • Enzyme Activators / therapeutic use*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / therapeutic use*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / genetics
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Protein Binding
  • Repressor Proteins / antagonists & inhibitors*
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Schistosoma / drug effects
  • Schistosoma / enzymology
  • Schistosomiasis / drug therapy
  • Structure-Activity Relationship


  • Enzyme Activators
  • Enzyme Inhibitors
  • Repressor Proteins
  • HDAC8 protein, human
  • Histone Deacetylases