Histone deacetylase inhibitors: design, structure-activity relationships and therapeutic implications for cancer

Anticancer Agents Med Chem. 2009 Jul;9(6):661-92. doi: 10.2174/187152009788679976.


Histone deacetylases (HDACs) remove acetyl groups from the tails of lysine residues of histone protein in nuclear chromatin and also from acetylated sites in non-histone proteins. HDACs and histone acetyltransferases (HATs) are major influences on the level of cellular protein acetylation, and an imbalance in acetylation levels, particularly under-acetylated (hypoacetylated) histone protein has been associated with precancerous or malignant states. Consequently, small molecule inhibitors of HDACs have been synthesised and some now form a newly emerging class of anti-cancer agents that can regulate transcription and inhibit proliferation of cancer cells by inducing cell cycle arrest, differentiation and/or apoptosis, among other major biological phenomena. The different mechanism(s) of action of HDAC inhibitors compared to conventional anti-neoplastic agents provides a possibility that HDAC inhibitors may be effective for refractory cancers. Accordingly, a number of programs for the development of HDAC inhibitors as anti-cancer drugs have been initiated. This review highlights recent developments in the design, synthesis and biological properties of HDAC inhibitors in the context of potential cancer therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use*
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases