A bid to revive MMP inhibitors
Matrix metalloproteinases, or MMPs, were once viewed as obvious drug targets-extracellular proteases that are selectively upregulated and play critical functional roles in many diseases. But MMP inhibitors failed in cancer trials a decade ago primarily because of poor specificity that led to severe musculoskeletal side effects. Now, researchers at the State University of New York at Stony Brookhave identified small molecule inhibitors specific for MMP9 that block its protein-protein interactions rather than itsproteolytic activity.1
The next steps for the Stony Brook team will be to design more potent inhibitors and convince potential partners the molecules have a clean safety profile.
Academics contacted by SciBXthink previous failures of MMP inhibitors-most notably marimastat from British Biotech plc2 (now part of Vernalis plc)-reflected a fundamental lack of biological and biochemical understanding of the targets.
"They didn't know the concentrations of inhibitors to use,