Discovery of histone deacetylase 8 selective inhibitors

Bioorg Med Chem Lett. 2011 May 1;21(9):2601-5. doi: 10.1016/j.bmcl.2011.01.134. Epub 2011 Feb 2.

Abstract

We have developed an efficient method for synthesizing candidate histone deacetylase (HDAC) inhibitors in 96-well plates, which are used directly in high-throughput screening. We selected building blocks having hydrazide, aldehyde and hydroxamic acid functionalities. The hydrazides were coupled with different aldehydes in DMSO. The resulting products have the previously identified 'cap/linker/biasing element' structure known to favor inhibition of HDACs. These compounds were assayed without further purification. HDAC8-selective inhibitors were discovered from this novel collection of compounds.

Publication types

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

MeSH terms

  • Biological Assay
  • Enzyme Activation / drug effects
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Repressor Proteins / antagonists & inhibitors*

Substances

  • Histone Deacetylase Inhibitors
  • Repressor Proteins
  • HDAC8 protein, human
  • Histone Deacetylases