Abstract
In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.
MeSH terms
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Antineoplastic Agents / therapeutic use
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Chelating Agents / pharmacology
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Chemistry, Pharmaceutical
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Drug Design
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Drug Screening Assays, Antitumor*
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Enzyme Inhibitors / pharmacology
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HeLa Cells
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Histone Deacetylase Inhibitors*
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Humans
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Ketones / chemistry*
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Models, Chemical
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Neoplasms / drug therapy
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Prodrugs / chemistry
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Structure-Activity Relationship
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Zinc / chemistry
Substances
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Antineoplastic Agents
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Chelating Agents
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Ketones
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Prodrugs
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Zinc