ONO-5046, a novel inhibitor of human neutrophil elastase

ONO-5046, N-[2-[4-(2,2-Dimethylpropionyloxy)phenylsulfonylamino] aminoacetic acid, competitively inhibited human neutrophil Elastase (IC50 = 0.044 microM, Ki = 0.2 microM). It also inhibited leukocyte Elastase obtained from rabbit, rat, hamster and mouse. However, ONO-5046 did not inhibit trypsin, Thrombin, plasmin, plasma Kallikrein, pancreas Kallikrein, chymotrypsin and Cathepsin G even at 100 microM. In in vivo studies, ONO-5046 suppressed lung hemorrhage in hamster (ID50 = 82 micrograms/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID50 = 9.6 mg/kg) by intravenous administration, both of which were induced by human neutrophil Elastase.