MASP2/3 inhibitors-2(Innoviva Specialty Therapeutics)

The complement system of innate immunity recognizes, opsonizes, and kills invading pathogens and damaged cells, and stimulates an inflammatory response. Inappropriate or excessive complement activity is associated with a wide variety of pathological conditions, and several drugs targeting complement components have been approved. Here we describe the discovery and structure-activity relationships of a novel class of 2-aminoimidazole-containing inhibitors of mannan-binding lectin-associated serine proteases -2 and -3 (MASP-2 and MASP-3), essential enzymes for activation of the lectin and alternative pathways of complement, respectively. With a high degree of target selectivity and favorable in vitro pharmacological properties, this inhibitor series has the potential to be developed as treatments for numerous diseases and pathological conditions.