Hurdles in the Drug Discovery of Cathepsin K Inhibitors

Title: Hurdles in the Drug Discovery of Cathepsin K Inhibitors

Volume: 10 Issue: 7

Author(s): Motohiko Kometani, Kazuhiko Nonomura, Takashi Tomoo and Satoru Niwa

Affiliation:

Keywords: Cathepsin K inhibitors, Species differences, PK/PD, On- and Off-target Side Effects, Osteoporosis, Bone resorption, Osteoclasts

Abstract: There were many hurdles in the drug discovery of cathepsin K inhibitors such as species differences not only in bone metabolism but also in amino acid sequences in the critical site of the target enzyme, discrepancies between PK/PD due to unique tissue distribution of the inhibitor affecting both efficacy and side effects originated from a characteristic intracellular or tissue distribution of some classes of compounds. The value of this new therapeutic approach over the launched indirect competitors should be further clarified from the efficacy and side effect point of view. The cathepsin K inhibitor drug discovery was initiated based on a strong and osteoclast-specific expression of this enzyme. However, the tissues and cells expressing cathepsin K have been expanding as the investigation on pathological conditions progressed with respect to side effects as well as new possible indications.

Cite this article as:

Kometani Motohiko, Nonomura Kazuhiko, Tomoo Takashi and Niwa Satoru, Hurdles in the Drug Discovery of Cathepsin K Inhibitors, Current Topics in Medicinal Chemistry 2010; 10 (7) . https://dx.doi.org/10.2174/156802610791113478