Challenges with matrix metalloproteinase inhibition and future drug discovery avenues.

Matrix metalloproteinases have been in the scope of pharmaceutical drug discovery for decades as promising targets for drug development. Until present, no modulator of the enzyme class survived clinical trials, all failing for various reasons. Nevertheless, the target family did not lose its attractiveness and there is ever more evidence that MMP modulators are likely to overcome the hurdles and result in successful clinical therapies. This review provides an overview of past efforts that were taken in the development of MMP inhibitors and insight into promising strategies that might enable drug discovery in the field in the future. Small molecule inhibitors as well as biomolecules are reviewed. Despite the lack of successful clinical trials in the past, there is ongoing research in the field of MMP modulation, proving the target class has not lost its appeal to pharmaceutical research. With ever-growing insights from different scientific fields that shed light on previously unknown correlations, it is now time to use synergies deriving from biological knowledge, chemical structure generation, and clinical application to reach the ultimate goal of bringing MMP derived drugs on a broad front for the benefit of patients into therapeutic use.