Rationalized computer-aided design of matrix metalloprotease-selective prodrugs
| Autor: | J. Jonathan Harburn, Robert A. Falconer, Caitlin A. Mooney, Mohit Jain, Jason H. Gill, David J. Berry, Paul M. Loadman, Steven L. Cobb |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Matrix metalloproteinase inhibitor Antineoplastic Agents Matrix Metalloproteinase Inhibitors Matrix metalloproteinase Molecular Docking Simulation Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Glioma Drug Discovery medicine Animals Humans Prodrugs Chemistry Prodrug medicine.disease Matrix Metalloproteinases In vitro 030104 developmental biology Cell culture Drug Design 030220 oncology & carcinogenesis Cancer research Computer-Aided Design Molecular Medicine |
| Zdroj: | Journal of medicinal chemistry, 2017, Vol.60(10), pp.4496-4502 [Peer Reviewed Journal] |
| Popis: | Matrix metalloproteinases (MMPs) are central to cancer development and metastasis. They are highly active in the tumour 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 tumour-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. |
| Databáze: | OpenAIRE |
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