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Inhibitors of cathepsin K: a patent review (2004 - 2010)

Jac Wijkmans1, Jan Gossen

  • 1Medicinal Chemistry Department, Merck Research Laboratories, MSD, PO Box 20, 5340 BH Oss, The Netherlands. jac.wijkmans@merck.com

Expert Opinion on Therapeutic Patents
|September 20, 2011
PubMed
Abstract

Insights

Cathepsin K inhibitors show promise for treating bone diseases like osteoporosis. Research from 2004-2010 focused on small molecules, with some progressing to clinical trials.

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Drug Discovery

Background:

  • Cathepsin K is a lysosomal cysteine protease crucial for osteoclast activity and bone resorption.
  • Inhibiting Cathepsin K offers a therapeutic strategy for bone resorption disorders, including osteoporosis.

Purpose of the Study:

  • To review low molecular weight Cathepsin K inhibitors from patent literature (2004-2010).
  • To survey different chemotypes and electrophilic warhead types.
  • To incorporate data from peer-reviewed journals and clinical investigations.

Main Methods:

  • Systematic review of patent literature from July 2004 to 2010.
  • Categorization of inhibitors by electrophilic warhead.
  • Inclusion of data from published research and clinical trials.

Main Results:

  • Over 50 patent applications filed between 2004-2010 indicate sustained interest.
  • Peptide-derived inhibitors with reversible nitrile or ketone warheads dominate.
  • ONO-5334 and odanacatib advanced to Phase II and III clinical trials, respectively.

Conclusions:

  • Continued interest in small molecule Cathepsin K inhibitors for therapeutic use.
  • Selectivity against off-target cathepsins is critical for clinical success.
  • Eliminating lysosomotropic properties may enhance inhibitor design.
  • Clinical trial outcomes for ONO-5334 and odanacatib will shape future therapeutic development.

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