The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor.
Publication
, Journal Article
Isabel, E; Bateman, KP; Chauret, N; Cromlish, W; Desmarais, S; Duong, LT; Falgueyret, J-P; Gauthier, JY; Lamontagne, S; Lau, CK; Léger, S ...
Published in: Bioorganic & medicinal chemistry letters
February 2010
MK-0674 is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib with a comparable inhibitory potency profile against Cat K. It is orally bioavailable and exhibits long half-life in pre-clinical species. In vivo studies using deuterated MK-0674 show stereoselective epimerization of the alcohol stereocenter via an oxidation/reduction cycle. From in vitro incubations, two metabolites could be identified: the hydroxyleucine and the glucuronide conjugate which were confirmed using authentic synthetic standards.
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Published In
Bioorganic & medicinal chemistry letters
DOI
EISSN
1464-3405
ISSN
0960-894X
Publication Date
February 2010
Volume
20
Issue
3
Start / End Page
887 / 892
Related Subject Headings
- Rats
- Rabbits
- Medicinal & Biomolecular Chemistry
- Macaca mulatta
- Humans
- Hepatocytes
- Drug Discovery
- Dogs
- Cysteine Proteinase Inhibitors
- Cathepsin K
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MLA
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Isabel, E., Bateman, K. P., Chauret, N., Cromlish, W., Desmarais, S., Duong, L. T., … Black, W. C. (2010). The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor. Bioorganic & Medicinal Chemistry Letters, 20(3), 887–892. https://doi.org/10.1016/j.bmcl.2009.12.083
Isabel, Elise, Kevin P. Bateman, Nathalie Chauret, Wanda Cromlish, Sylvie Desmarais, Le T. Duong, Jean-Pierre Falgueyret, et al. “The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor.” Bioorganic & Medicinal Chemistry Letters 20, no. 3 (February 2010): 887–92. https://doi.org/10.1016/j.bmcl.2009.12.083.
Isabel E, Bateman KP, Chauret N, Cromlish W, Desmarais S, Duong LT, et al. The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor. Bioorganic & medicinal chemistry letters. 2010 Feb;20(3):887–92.
Isabel, Elise, et al. “The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor.” Bioorganic & Medicinal Chemistry Letters, vol. 20, no. 3, Feb. 2010, pp. 887–92. Epmc, doi:10.1016/j.bmcl.2009.12.083.
Isabel E, Bateman KP, Chauret N, Cromlish W, Desmarais S, Duong LT, Falgueyret J-P, Gauthier JY, Lamontagne S, Lau CK, Léger S, LeRiche T, Lévesque J-F, Li CS, Massé F, McKay DJ, Mellon C, Nicoll-Griffith DA, Oballa RM, Percival MD, Riendeau D, Robichaud J, Rodan GA, Rodan SB, Seto C, Thérien M, Truong VL, Wesolowski G, Young RN, Zamboni R, Black WC. The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor. Bioorganic & medicinal chemistry letters. 2010 Feb;20(3):887–892.
Published In
Bioorganic & medicinal chemistry letters
DOI
EISSN
1464-3405
ISSN
0960-894X
Publication Date
February 2010
Volume
20
Issue
3
Start / End Page
887 / 892
Related Subject Headings
- Rats
- Rabbits
- Medicinal & Biomolecular Chemistry
- Macaca mulatta
- Humans
- Hepatocytes
- Drug Discovery
- Dogs
- Cysteine Proteinase Inhibitors
- Cathepsin K