American Chemical Society
jm6b01472_si_002.csv (0.7 kB)

Rationalized Computer-Aided Design of Matrix-Metalloprotease-Selective Prodrugs

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posted on 2017-05-04, 00:00 authored by Mohit Jain, J. Jonathan Harburn, Jason H. Gill, Paul M. Loadman, Robert A. Falconer, Caitlin A. Mooney, Steven L. Cobb, David J. Berry
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.