Abstract
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
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Benzene Derivatives / chemical synthesis*
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Benzene Derivatives / chemistry
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Benzene Derivatives / pharmacology*
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Binding Sites / drug effects
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylase Inhibitors*
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Histone Deacetylases / chemistry
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Histone Deacetylases / metabolism
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Humans
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Models, Molecular*
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Molecular Structure
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Protein Isoforms
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Repressor Proteins
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Structure-Activity Relationship
Substances
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Benzene Derivatives
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Histone Deacetylase Inhibitors
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Protein Isoforms
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Repressor Proteins
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HDAC1 protein, human
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Histone Deacetylase 1
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Histone Deacetylase 2
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Histone Deacetylases