2. Academic Validation
  3. The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor

The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor

  • Bioorg Med Chem Lett. 2010 Feb 1;20(3):887-92. doi: 10.1016/j.bmcl.2009.12.083.
Elise Isabel 1,  Kevin P Bateman,  Nathalie Chauret,  Wanda Cromlish,  Sylvie Desmarais,  Le T Duong,  Jean-Pierre Falgueyret,  Jacques Yves Gauthier,  Sonia Lamontagne,  Cheuk K Lau,  Serge Léger,  Tammy LeRiche,  Jean-François Lévesque,  Chun Sing Li,  Frédéric Massé,  Daniel J McKay,  Christophe Mellon,  Deborah A Nicoll-Griffith,  Renata M Oballa,  M David Percival,  Denis Riendeau,  Joël Robichaud,  Gideon A Rodan,  Sevgi B Rodan,  Carmai Seto,  Michel Thérien,  Vouy Linh Truong,  Gregg Wesolowski,  Robert N Young,  Robert Zamboni,  W Cameron Black
Affiliations

Affiliation

  • 1 Merck Frosst Centre for Therapeutic Research, 16711 TransCanada Hwy, Kirkland, Québec, Canada H9H 3L1. elise_isabel@merck.com
PMID: 20061146 DOI: 10.1016/j.bmcl.2009.12.083
Abstract

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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