Rationalized computer-aided design of matrix metalloprotease-selective prodrugs.

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