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Potent and Selective Cathepsin L Inhibitors Do Not Inhibit Human Osteoclast Resorption in Vitro
Cathepsins K and L are related cysteine proteases that have been proposed to play important roles in osteoclast-mediated bone resorption. To further examine the putative role of cathepsin L in bone resorption, we have evaluated selective and potent inhibitors of human cathepsin L and cathepsin K in...
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Published in: | The Journal of biological chemistry 2001-04, Vol.276 (15), p.11507-11511 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Cathepsins K and L are related cysteine proteases that have been proposed to play important roles in osteoclast-mediated bone resorption. To further examine the putative role of cathepsin L in bone resorption, we have evaluated selective and potent inhibitors of human cathepsin L and cathepsin K in an in vitro assay of human osteoclastic resorption and an in situ assay of osteoclast cathepsin activity. The potent selective cathepsin L inhibitors (Ki = 0.0099, 0.034, and 0.27 nm) were inactive in both the in situcytochemical assay (IC50 > 1 μm) and the osteoclast-mediated bone resorption assay (IC50 > 300 nm). Conversely, the cathepsin K selective inhibitor was potently active in both the cytochemical (IC50 = 63 nm) and resorption (IC50 = 71 nm) assays. A recently reported dipeptide aldehyde with activity against cathepsins L (Ki = 0.052 nm) and K (Ki = 1.57 nm) was also active in both assays (IC50 = 110 and 115 nm, respectively) These data confirm that cathepsin K and not cathepsin L is the major protease responsible for human osteoclastic bone resorption. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M010684200 |