Abstract
A series of small molecules bearing an alpha-ketoamide warhead were synthesized and evaluated for their ability to inhibit cathepsin S, a key proteolytic enzyme upregulated in many cancers during tumor progression and metastasis. Most of the synthetic compounds were noncytotoxic, but several robustly inhibited cathepsin S (IC(50) < 10 nM) and potently suppressed cell migration, invasion, and capillary tube formation. These results highlight the potential of alpha-ketoamide therapy for preventing or delaying cancer spread.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology*
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Amides / therapeutic use
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Cathepsins / antagonists & inhibitors*
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Cathepsins / chemistry
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Cell Line, Tumor
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Drug Design*
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Humans
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Models, Molecular
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Neoplasm Invasiveness
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Neoplasms / blood supply*
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Neoplasms / enzymology
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Neoplasms / pathology*
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Neoplasms / physiopathology
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Neovascularization, Pathologic / drug therapy*
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology
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Protease Inhibitors / therapeutic use
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Protein Conformation
Substances
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Amides
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Protease Inhibitors
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Cathepsins
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cathepsin S