Abstract
Odanacatib is a potent, selective, and neutral cathepsin K inhibitor which was developed to address the metabolic liabilities of the Cat K inhibitor L-873724. Substituting P1 and modifying the P2 side chain led to a metabolically robust inhibitor with a long half-life in preclinical species. Odanacatib was more selective in whole cell assays than the published Cat K inhibitors balicatib and relacatib. Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors.
MeSH terms
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Animals
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Azepines / chemistry
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Azepines / pharmacology
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Biphenyl Compounds / pharmacology*
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Cathepsin K
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Cathepsins / antagonists & inhibitors*
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Collagen / drug effects
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Collagen / immunology
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Cysteine Proteinase Inhibitors / pharmacology*
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Dogs
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Fibroblasts / drug effects
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Humans
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Models, Biological
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Molecular Structure
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Osteoporosis, Postmenopausal / drug therapy
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Skin / cytology
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Structure-Activity Relationship
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Sulfones / chemistry
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Sulfones / pharmacology
Substances
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Azepines
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Biphenyl Compounds
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Cysteine Proteinase Inhibitors
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L-873724
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Sulfones
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Collagen
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relacatib
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Cathepsins
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CTSK protein, human
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Cathepsin K
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odanacatib