Phosphorus based inhibitors of matrix metalloproteinases

This article reviews the current state of phosphorus-based matrix metalloproteinase (MMP) inhibitors. MMPs are a potentially harmful group of enzymes and their successful inhibition can be expected to alleviate a large diversity of severe pathologies that are listed in the beginning of the review. More than 20 years of worldwide search by the scientific and industrial community for a clinically useful inhibitor have resulted in failure because of toxic side effects or lack of in vivo efficacy of the tested molecules. In the majority of inhibitors reviewed in this article, the phosphorus plays the role of zinc bonding, as most MMP inhibitors are designed to do, since the catalytic zinc ion is crucial for the functioning of these enzymes. The main classes of phosphorus based MMP inhibitors are: bisphosphonates, phosphonamidates, phosphinamidates, phosphinates, phosphonates and carbamoylphosphonates.