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 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.