Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1:2)

Bioorg Med Chem Lett. 2008 Feb 1;18(3):973-8. doi: 10.1016/j.bmcl.2007.12.031. Epub 2008 Jan 7.


We report herein the initial exploration of novel selective HDAC1/HDAC2 inhibitors (SHI-1:2). Optimized SHI-1:2 structures exhibit enhanced intrinsic activity against HDAC1 and HDAC2, and are greater than 100-fold selective versus other HDACs, including HDAC3. Based on the SAR of these agents and our current understanding of the HDAC active site, we postulate that the SHI-1:2 extend the existing HDAC inhibitor pharmacophore to include an internal binding domain.

MeSH terms

  • Benzene Derivatives / chemical synthesis*
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology*
  • Binding Sites / drug effects
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Humans
  • Models, Molecular*
  • Molecular Structure
  • Protein Isoforms
  • Repressor Proteins
  • Structure-Activity Relationship


  • Benzene Derivatives
  • Histone Deacetylase Inhibitors
  • Protein Isoforms
  • Repressor Proteins
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylases