A series of novel, potent, and selective histone deacetylase inhibitors

Bioorg Med Chem Lett. 2006 Dec 1;16(23):5948-52. doi: 10.1016/j.bmcl.2006.09.002. Epub 2006 Sep 20.


Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates.

MeSH terms

  • Amides / chemistry
  • Amino Acids / chemistry
  • Cell Line
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / classification
  • Enzyme Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Humans
  • Indoles / chemistry
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Molecular Structure
  • Sensitivity and Specificity
  • Structure-Activity Relationship


  • Amides
  • Amino Acids
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Indoles
  • Isoenzymes
  • Histone Deacetylases