Rationalized Computer-Aided design of Matrix Metalloprotease-Selective Prodrugs

Jain, M.; Harburn, J.J.; Gill, J.H.; Loadman, P.M.; Falconer, R.A.; Mooney, C.; Cobb, S.L.; Berry, D.J.

Abstract

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.

Citation

Jain, M., Harburn, J., Gill, J., Loadman, P., Falconer, R., Mooney, C., …Berry, D. (2017). Rationalized Computer-Aided design of Matrix Metalloprotease-Selective Prodrugs. Journal of Medicinal Chemistry, 60(10), 4496-4502. https://doi.org/10.1021/acs.jmedchem.6b01472

• Journal Article Type: Article
• Acceptance Date: May 5, 2017
• Online Publication Date: May 4, 2017
• Publication Date: May 25, 2017
• Deposit Date: May 9, 2017
• Publicly Available Date: May 4, 2018
• Journal: Journal of Medicinal Chemistry
• Print ISSN: 0022-2623
• Electronic ISSN: 1520-4804
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 60
• Issue: 10
• Pages: 4496-4502
• DOI: https://doi.org/10.1021/acs.jmedchem.6b01472
• Public URL: https://durham-repository.worktribe.com/output/1379856