Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 18, Issue 3, Pages 923-928Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2007.12.047
Keywords
cathepsin K; cysteine protease; odanacatib; MK-0822; osteoporosis
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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. (C) 2008 Elsevier Ltd. All rights reserved.
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