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Selective non zinc binding inhibitors of MMP13.
De Savi, Chris; Morley, Andrew D; Ting, Attilla; Nash, Ian; Karabelas, Kostas; Wood, Christine M; James, Michael; Norris, Stephen J; Karoutchi, Galith; Rankine, Neil; Hamlin, Gordon; Macfaul, Philip A; Ryan, David; Baker, Sarah V; Hargreaves, David; Gerhardt, Stefan.
Bioorg Med Chem Lett ; 21(14): 4215-9, 2011 Jul 15.
Article in English | MEDLINE | ID: mdl-21669521

ABSTRACT

Directed screening has identified a novel series of MMP13 inhibitors that possess good levels of activity whilst possessing excellent selectivity over related MMPs. The binding mode of the series has been solved by co-crystallisation and demonstrates an interesting mode of inhibition without interaction with the catalytic zinc atom.


Subject(s)
Matrix Metalloproteinase Inhibitors , Protease Inhibitors/chemistry , Zinc/chemistry , Binding Sites , Catalytic Domain , Crystallography, X-Ray , Matrix Metalloproteinase 13/metabolism , Protease Inhibitors/chemical synthesis , Protease Inhibitors/pharmacology , Stereoisomerism , Structure-Activity Relationship
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