title: Inhibitors of cathepsin K: a patent review (2004 - 2010).
abstract: BACKGROUND
  Cathepsin K is a lysosomal cysteine protease involved in osteoclast-mediated bone resorption. Inhibition of cathepsin K represents a potentially attractive therapeutic approach for treating diseases characterized by excessive bone resorption, such as osteoporosis.
  
  
  METHODS
  The present review provides an overview of low molecular weight cathepsin K inhibitors published in the patent literature from July 2004 to 2010. Different chemotypes are surveyed and listed according to electrophilic warhead type. Relevant information from original research articles in peer-reviewed journals and clinical investigations is also described.
  
  
  CONCLUSIONS
  Between 2004 and 2010, more than 50 patent applications have appeared, underlining the continued interest in small molecule cathepsin K inhibition for therapeutic intervention. Most compounds claimed are peptide-derived inhibitors displaying a reversible binding nitrile or ketone warhead. The success of these compounds in the clinic will be determined by the selectivity that can be achieved against other off-target cathepsin. In this respect, eliminating lysosomotropic characteristics may prove to be crucial in the design of selective cathepsin K inhibitors. During the review period, ONO-5334 and odanacatib have progressed to Phase II and Phase III clinical trials, respectively. The results of these studies are eagerly awaited and may determine the future of these agents as disease-modifying therapeutics.
authors.affiliation: Medicinal Chemistry Department, Merck Research Laboratories, MSD, PO Box 20, 5340 BH Oss, The Netherlands. jac.wijkmans@merck.com
authors.forename: Jac
authors.initials: J
authors.lastname: Wijkmans
authors.forename: Jan
authors.initials: J
authors.lastname: Gossen
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000503:physiopathology; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology; D010330:Patents as Topic
chemical_list: D056657:Cathepsin K