1TU6

Cathepsin K complexed with a ketoamide inhibitor

Summary for 1TU6

• Entry DOI: 10.2210/pdb1tu6/pdb
• Descriptor: Cathepsin K, SULFATE ION, [1-(4-FLUOROBENZYL)CYCLOBUTYL]METHYL (1S)-1-[OXO(1H-PYRAZOL-5-YLAMINO)ACETYL]PENTYLCARBAMATE, ... (4 entities in total)
• Functional Keywords: catk, cysteine protease, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P43235
• Total number of polymer chains: 2
• Total formula weight: 48224.15

Authors

Barrett, D.G.,Catalano, J.G.,Deaton, D.N.,Hassell, A.M.,Long, S.T.,Miller, A.B.,Miller, L.R.,Shewchuk, L.M.,Wells-Knecht, K.J.,Wright, L.L. (deposition date: 2004-06-24, release date: 2004-09-21, Last modification date: 2024-11-20)

Primary citation

Barrett, D.G.,Catalano, J.G.,Deaton, D.N.,Hassell, A.M.,Long, S.T.,Miller, A.B.,Miller, L.R.,Shewchuk, L.M.,Wells-Knecht, K.J.,Willard, D.H.,Wright, L.L.
Potent and selective P2-P3 ketoamide inhibitors of cathepsin K with improved pharmacokinetic properties via favorable P1', P1, and/or P3 substitutions
BIOORG.MED.CHEM.LETT., 14:4897-4902, 2004

PubMed Abstract: 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.

PubMed: 15341947
DOI: 10.1016/j.bmcl.2004.07.031

Experimental method

X-RAY DIFFRACTION (1.75 Å)