Brensocatib. Dipeptidyl peptidase 1 (DPP1) inhibitor, Treatment of non-cystic fibrosis bronchiectasis

Neutrophils, which are among the first immune cells to respond to both infection and injury, when activated can release pre-stored serine proteases such as neutrophil elastase, cathepsin G and proteinase 3. An abundant release of these proteolytic enzymes in the alveolar compartment as well as the airways can trigger collateral pulmonary tissue damage. Indeed, much of the tissue destruction that characterizes non-cystic fibrosis bronchiectasis appears to be caused by serine proteases. The transitory pharmacological inhibition of bone marrow dipeptidyl peptidase 1 (DPP1), which converts neutrophil proteolytic enzymes into their mature active form, is a therapeutic possibility to decrease the constitutively produced serine protease pool of neutrophils. Brensocatib (also called INS-1007 or AZD-7986) is a potent reversible DPP1 inhibitor that has been successfully evaluated in a phase II trial as a treatment for non-cystic fibrosis bronchiectasis and, consequently, has been granted breakthrough therapy designation by the U.S. Food and Drug Administration and Priority Medicines (PRIME) designation by the European Medicines Agency.