Isoform-selective histone deacetylase inhibitors

Curr Pharm Des. 2008;14(6):529-44. doi: 10.2174/138161208783885335.

Abstract

Histone deacetylases (HDACs) catalyze the deacetylation of the acetylated lysine residues of histones and non-histone proteins, and are involved in various fundamental life phenomena, such as gene expression and cell cycle progression. Thus far, eighteen HDAC family members have been identified and they can be divided into two categories, i.e., zinc-dependent enzymes (HDAC1-11) and NAD(+)-dependent enzymes (SIRT1-7). Some of the HDAC isoforms have important roles in cell functions, and are associated with various disease states, including cancer. Therefore, isoform-selective HDAC inhibitors are of great interest, not only as tools for probing the biological functions of the isoforms, but also as candidate therapeutic agents with few side effects. In this review, we cover isoform-selective HDAC inhibitors, including their biochemical and pharmacological functions.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Histone Deacetylases / physiology
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Isoenzymes / physiology
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Isoenzymes
  • Histone Deacetylases