The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K

  • Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8. doi: 10.1016/j.bmcl.2007.12.047.
Jacques Yves Gauthier  1 ,  Nathalie Chauret ,  Wanda Cromlish ,  Sylvie Desmarais ,  Le T Duong ,  Jean-Pierre Falgueyret ,  Donald B Kimmel ,  Sonia Lamontagne ,  Serge Léger ,  Tammy LeRiche ,  Chun Sing Li ,  Frédéric Massé ,  Daniel J McKay ,  Deborah A Nicoll-Griffith ,  Renata M Oballa ,  James T Palmer ,  M David Percival ,  Denis Riendeau ,  Joel Robichaud ,  Gideon A Rodan ,  Sevgi B Rodan ,  Carmai Seto ,  Michel Thérien ,  Vouy-Linh Truong ,  Michael C Venuti ,  Gregg Wesolowski ,  Robert N Young ,  Robert Zamboni ,  W Cameron Black
Affiliations
  • 1. Merck Frosst Centre for Therapeutic Research, 16711 TransCanada Hwy, Kirkland, Que., Canada.
PMID: 18226527 DOI: 10.1016/j.bmcl.2007.12.047
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.

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