2AUX

Cathepsin K complexed with a semicarbazone inhibitor

Summary for 2AUX

• Entry DOI: 10.2210/pdb2aux/pdb
• Related: 2AUZ
• Descriptor: Cathepsin K, (1R)-2-METHYL-1-(PHENYLMETHYL)PROPYL[(1S)-1-FORMYLPENTYL]CARBAMATE (3 entities in total)
• Functional Keywords: catk, cysteine protease, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Lysosome: P43235
• Total number of polymer chains: 1
• Total formula weight: 23828.89

Authors

Adkison, K.K.,Barrett, D.G.,Deaton, D.N.,Gampe, R.T.,Hassell, A.M.,Long, S.T.,McFadyen, R.B.,Miller, A.B.,Miller, L.R.,Shewchuk, L.M. (deposition date: 2005-08-29, release date: 2006-08-08, Last modification date: 2024-10-30)

Primary citation

Adkison, K.K.,Barrett, D.G.,Deaton, D.N.,Gampe, R.T.,Hassell, A.M.,Long, S.T.,McFadyen, R.B.,Miller, A.B.,Miller, L.R.,Payne, J.A.,Shewchuk, L.M.,Wells-Knecht, K.J.,Willard, D.H.,Wright, L.L.
Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?
Bioorg.Med.Chem.Lett., 16:978-983, 2006

PubMed Abstract: Starting from potent aldehyde inhibitors with poor drug properties, derivatization to semicarbazones led to the identification of a series of semicarbazone-based cathepsin K inhibitors with greater solubility and better pharmacokinetic profiles than their parent aldehydes. Furthermore, a representative semicarbazone inhibitor attenuated bone resorption in an ex vivo rat calvarial bone resorption model. However, based on enzyme inhibition comparisons at neutral pH, semicarbazone hydrolysis rates, and 13C NMR experiments, these semicarbazones probably function as prodrugs of aldehydes.

PubMed: 16290936
DOI: 10.1016/j.bmcl.2005.10.108

Experimental method

X-RAY DIFFRACTION (2.4 Å)