Naturally occurring small molecule compounds that target histone deacetylases and their potential applications in cancer therapy

J Antibiot (Tokyo). 2021 Oct;74(10):667-676. doi: 10.1038/s41429-021-00459-6. Epub 2021 Aug 23.

Abstract

Epigenetics is defined as the heritable alteration of gene expression without change to the DNA sequence. Epigenetic abnormalities play a role in various diseases, including cancer. Epigenetic regulation of gene expression occurs through histone chemical modifications and DNA methylation. Lysine acetylation is one of the major histone chemical modifications essential for epigenetic gene expression. Histone acetylation is reversibly regulated by histone acetyltransferases and histone deacetylases, which are molecular targets for cancer therapy. There has been an explosion of research in epigenetic-related drug discovery, and accordingly many small molecule compounds have been developed. Notably, several small molecule inhibitors of histone deacetylases have been approved for the treatment of cancer. This review will introduce natural products, their derivative inhibitors of histone deacetylases, and their clinical development.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Biological Products
  • Histone Deacetylase Inhibitors