2aux
Cathepsin K complexed with a semicarbazone inhibitor
OverviewOverview
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.
About this StructureAbout this Structure
2AUX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Semicarbazone-based inhibitors of cathepsin K, are they prodrugs for aldehyde inhibitors?, Adkison KK, Barrett DG, Deaton DN, Gampe RT, Hassell AM, Long ST, McFadyen RB, Miller AB, Miller LR, Payne JA, Shewchuk LM, Wells-Knecht KJ, Willard DH Jr, Wright LL, Bioorg Med Chem Lett. 2006 Feb 15;16(4):978-83. Epub 2005 Nov 15. PMID:16290936 Page seeded by OCA on Sat May 3 19:30:22 2008