Design of selective histone deacetylase inhibitors: rethinking classical pharmacophore

Future Med Chem. 2018 Jul 1;10(13):1537-1540. doi: 10.4155/fmc-2018-0125. Epub 2018 Jul 3.

Abstract

For two decades, a classical pharmacophore model comprising a zinc binding group, a linker and a cap group, has been used for the development of histone deacetylase (HDAC) inhibitors. However, some of the recently reported selective HDAC inhibitors targeting additional, usually subtype specific, cavities in the binding pocket show supplementary features which do not fit this classical pharmacophore. We, therefore, propose an extended pharmacophore model, which can describe almost all currently known HDAC inhibitors. This pharmacophore consists of six pharmacophoric features and should be helpful for the classification and design of selective HDAC inhibitors.

Publication types

  • Editorial

MeSH terms

  • Binding Sites
  • Drug Design*
  • Drug Discovery
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism*
  • Humans

Substances

  • Histone Deacetylase Inhibitors
  • Histone Deacetylases