Selective non zinc binding inhibitors of MMP13

Chris De Savi; Andrew D Morley; Attilla Ting; Ian Nash; Kostas Karabelas; Christine M Wood; Michael James; Stephen J Norris; Galith Karoutchi; Neil Rankine; Gordon Hamlin; Philip A Macfaul; David Ryan; Sarah V Baker; David Hargreaves; Stefan Gerhardt

doi:10.1016/j.bmcl.2011.05.075

Selective non zinc binding inhibitors of MMP13

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4215-9. doi: 10.1016/j.bmcl.2011.05.075. Epub 2011 May 27.

Authors

Chris De Savi¹, Andrew D Morley, Attilla Ting, Ian Nash, Kostas Karabelas, Christine M Wood, Michael James, Stephen J Norris, Galith Karoutchi, Neil Rankine, Gordon Hamlin, Philip A Macfaul, David Ryan, Sarah V Baker, David Hargreaves, Stefan Gerhardt

Affiliation

¹ AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.

PMID: 21669521
DOI: 10.1016/j.bmcl.2011.05.075

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.

MeSH terms

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

Substances

Matrix Metalloproteinase Inhibitors
Protease Inhibitors
Matrix Metalloproteinase 13
Zinc