Abstract
The FDA-approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat) was modified to improve its selectivity for a single histone deaetylase (HDAC) isoform. We show that attaching an ethyl group at the C3 position transforms SAHA from nonselective to an HDAC6-selective inhibitor. Theses results indicate that small structural changes in SAHA can significantly influence selectivity, which will lead future anti-cancer design efforts targeting HDAC proteins.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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HeLa Cells
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Histone Deacetylase Inhibitors / chemistry*
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Histone Deacetylase Inhibitors / pharmacology*
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Histone Deacetylases / metabolism
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Humans
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Hydroxamic Acids / chemistry*
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Hydroxamic Acids / pharmacology*
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Neoplasms / drug therapy
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Protein Isoforms / metabolism
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Vorinostat
Substances
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Antineoplastic Agents
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Protein Isoforms
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Vorinostat
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Histone Deacetylases