Alvelestat

BeschreibungAZD 9668 is an orally bioavailable inhibitor of neutrophil elastase (IC50 = 12 nM for the human enzyme). It is greater than 600-fold selective for neutrophil elastase over other serine proteases, including human proteinase-3 and cathepsin G, bovine trypsin and chymotrypsin, and porcine pancreatic elastase. AZD 9668 inhibits neutrophil elastase activity in zymosan-stimulated isolated whole blood and in cell-associated assays (IC50s = 46 and 48 nM, respectively). It decreases the number of neutrophils in bronchoalveolar lavage fluid (BALF) in a mouse model of smoke-induced airway inflammation when administered at a dose of 6 mg/kg. AZD 9668 also prevents airspace enlargement and small airway remodeling in a guinea pig model of chronic smoke-induced inflammation and emphysema.