Abstract
A series of hydroxamate based HDAC inhibitors containing a phenylisoxazole as the CAP group has been synthesized using nitrile oxide cycloaddition chemistry. An HDAC6 selective inhibitor having a potency of approximately 2 picomolar was identified. Some of the compounds were examined for their ability to block pancreatic cancer cell growth and found to be about 10-fold more potent than SAHA. This research provides valuable, new molecular probes for use in exploring HDAC biology.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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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 Probes / chemical synthesis*
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Molecular Probes / chemistry
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Molecular Probes / classification
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Molecular Probes / pharmacology*
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Molecular Structure
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Nitriles / chemistry*
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Oxides / chemistry*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Molecular Probes
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Nitriles
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Oxides
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Histone Deacetylases