Cathepsin K complexed with a ketoamide inhibitor
[CATK_HUMAN] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:265800]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.   
[CATK_HUMAN] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.
Publication Abstract from PubMed
A series of ketoamides were synthesized and evaluated for inhibitory activity against cathepsin K. Exploration of the interactions between achiral P(2) substituents and the cysteine protease based on molecular modelling suggestions resulted in potent cathepsin K inhibitors that demonstrated high selectivity versus cathepsins B, H, and L. Subsequent modifications of the P(3), P(1), and P(1') moieties afforded orally bioavailable inhibitors.
Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with good pharmacokinetic properties via favorable P1', P1, and/or P3 substitutions.,Barrett DG, Catalano JG, Deaton DN, Hassell AM, Long ST, Miller AB, Miller LR, Shewchuk LM, Wells-Knecht KJ, Willard DH Jr, Wright LL Bioorg Med Chem Lett. 2004 Oct 4;14(19):4897-902. PMID:15341947
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.