Histone deacetylase inhibitors: discovery and development as anticancer agents

Expert Opin Investig Drugs. 2005 Dec;14(12):1497-511. doi: 10.1517/13543784.14.12.1497.

Abstract

Histone deacetylase (HDAC) inhibitors are a new class of targeted anticancer agents. Several HDAC inhibitors are in clinical trials and have shown significant activity against a spectrum of both haematological and solid tumours at doses that are well tolerated by patients. HDACs and histone acetyltransferases can, by reversible acetylation, modify the structure and function of histones and proteins in transcription factor complexes, which are involved in the regulation of gene expression, as well as many non-histone proteins that are involved in regulating cell proliferation and cell death. HDAC inhibitors are a structurally diverse group of molecules; these agents selectively alter the expression of genes. HDAC inhibitors can induce cancer cell death, whereas normal cells are relatively resistant to HDAC inhibitor-induced cell death.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Drug Design*
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors*
  • Humans

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors