Abstract
A novel series of ketoamide-based inhibitors of cathepsin K has been identified. Modifications to P(2) and P(3) elements were crucial to enhancing inhibitory activity. Although not optimized, a selected inhibitor was effective in attenuating type I collagen hydrolysis in a surrogate assay of bone resorption.
MeSH terms
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Bone Resorption / metabolism*
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Bone and Bones / drug effects*
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Bone and Bones / pathology
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Cathepsin K
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Cathepsins / antagonists & inhibitors*
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Collagen Type I / metabolism*
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Cysteine Proteinase Inhibitors / chemical synthesis*
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Cysteine Proteinase Inhibitors / pharmacology*
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Drug Design
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Humans
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Hydrolysis
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Structure-Activity Relationship
Substances
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Collagen Type I
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Cysteine Proteinase Inhibitors
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Cathepsins
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CTSK protein, human
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Cathepsin K