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

      Jain, M.; Harburn, J.J.; Gill, Jason H.; Loadman, Paul M.; Falconer, Robert A.; Mooney, C.A.; Cobb, S.L.; Berry, David J. (2017-05-25)
      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.