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On the inhibition of histone deacetylase 8.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2010 Jun 01; Vol. 18 (11), pp. 4103-10. Date of Electronic Publication: 2010 Apr 03. - Publication Year :
- 2010
-
Abstract
- Histone deacetylases are key regulators of gene expression and have recently emerged as important therapeutic targets for cancer and a growing number of non-malignant diseases. Many widely studied inhibitors of HDACs such as SAHA are thought to have low selectivity within or between the human HDAC isoform classes. Using an isoform-selective assay, we have shown that a number of the known inhibitors have in fact a low activity against HDAC8. Based on the wealth of structural information available for human HDAC8, we use a combination of docking and molecular dynamics simulations to determine the structural origin of the experimental results. A close relationship is found between the activity and the high surface malleability of HDAC8. These results provide a rationale for the recently described 'linkerless' HDAC8 selective inhibitors and design criteria for HDAC8 selective inhibitors.
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 18
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20472442
- Full Text :
- https://doi.org/10.1016/j.bmc.2010.03.080