Abstract
Discovery and optimization of potency and selectivity of a non-Zn-chelating MMP-13 inhibitor with the aid of protein co-crystal structural information is reported. This inhibitor was observed to have a binding mode distinct from previously published MMP-13 inhibitors. Potency and selectivity were improved by extending the hit structure out from the active site into the S1' pocket.
MeSH terms
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Catalytic Domain
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Chelating Agents / chemistry
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Chelating Agents / pharmacology*
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Matrix Metalloproteinase 13 / chemistry
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Matrix Metalloproteinase 13 / metabolism*
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Matrix Metalloproteinase Inhibitors*
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Models, Molecular
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Protein Binding
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Structure-Activity Relationship
Substances
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Chelating Agents
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Matrix Metalloproteinase Inhibitors
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Protease Inhibitors
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Matrix Metalloproteinase 13