Abstract
Matrix metalloproteinases (MMPs) are central to cancer development and metastasis. They are highly active in the tumor environment and absent or inactive in normal tissues; therefore they represent viable targets for cancer drug discovery. In this study we evaluated in silico docking to develop MMP-subtype-selective tumor-activated prodrugs. Proof of principle for this therapeutic approach was demonstrated in vitro against an aggressive human glioma model, with involvement of MMPs confirmed using pharmacological inhibition.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Computer-Aided Design*
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Drug Design*
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Glioma / drug therapy
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Glioma / enzymology
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Humans
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Matrix Metalloproteinase Inhibitors / chemistry*
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Matrix Metalloproteinase Inhibitors / pharmacology*
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Matrix Metalloproteinases / chemistry
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Matrix Metalloproteinases / metabolism*
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Mice
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Molecular Docking Simulation
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Prodrugs / chemistry*
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Prodrugs / pharmacology*
Substances
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Antineoplastic Agents
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Matrix Metalloproteinase Inhibitors
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Prodrugs
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Matrix Metalloproteinases