Mast cell tryptase as a target for drug design

Human mast cell tryptase-beta, a tryptic serine protease with a unique structure, is an interesting therapeutic target that several companies and institutions have targeted for drug discovery. The catalytic activity of this tryptic enzyme has been linked to many disease states and proinflammatory events; however, the physical and physiological differences of tryptase across various species have made animal model data difficult to interpret, particularly in the context of human disease. Still, both protein and small-molecule tryptase inhibitors have been reported and the X-ray crystal structure of the enzyme aids in understanding how these compounds might bind. Three modes of inhibition exist: monofunctional inhibition, bifunctional inhibition and tetramer disruption. Many of these inhibitors have demonstrated activity in animal models. Human clinical studies have been conducted or are under way with certain tryptase inhibitors.