Abstract
Histone deacetylase (HDAC) inhibitors have potential for cancer therapy. An HDAC inhibitor based on a cyclic peptide mimic of known structure, linked by an aliphatic chain to a hydroxamic acid, was designed and synthesized. The chimeric compound showed potent competitive inhibition of nuclear HDACs, with an IC50 value of 46 nM and a Ki value of 13.7 nM. The designed inhibitor showed 4-fold selectivity for HDAC1 (57 nM) over HDAC8 (231 nM).
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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Biomimetics
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Drug Design
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HeLa Cells
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Histone Deacetylase Inhibitors*
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Histone Deacetylases / chemistry
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Humans
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Hydroxamic Acids / chemical synthesis*
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology
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Models, Molecular
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Molecular Structure
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Nuclear Proteins / antagonists & inhibitors*
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Nuclear Proteins / chemistry
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Peptides, Cyclic / chemical synthesis*
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology
Substances
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Nuclear Proteins
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Peptides, Cyclic
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Histone Deacetylases