Myeloperoxidase (MPO): Do We Need Inhibitors?

Neutrophils, monocytes and selected tissue macrophages are the predominant sources of myeloperoxidase (MPO). Under physiological chloride concentration, the MPO hemo protein can catalyze the reaction of formation of hypochlorous acid in presence of another oxidant, hydrogen peroxide. MPO-mediated oxidants play a significant part in the inflammatory response, though, the MPO is traditionally viewed as an unspecific microbicidal enzyme and some intermediates are important for immune defense system against invading pathogens. Inflammation plays a lead role in the manifestation and the amelioration of atherosclerosis and other cardiovascular diseases. Hence, there is continuing interest on MPO as a target in the diagnosis and development of potent therapeutic aid against this oxidative enzyme. The necessity of developing a drug to inhibit MPO is getting steady momentum and through this review, we assess the current status of the literature on the source of MPO, its primary physiological role, currently available inhibitors and application of in silico screening, harmful effects on the increased levels of MPO and its implication in multiple disease progression. We critically analyze current efforts toward the development of suitable inhibitors using small organic molecules, unexplored organometallic scaffolds, utilization of aptamers as myeloperoxidase inhibitor and future perspective on the scope of therapeutic intervention for this attractive target.