ONO-5046, a novel inhibitor of human neutrophil elastase
Abstract
ONO-5046, N-[2-[4-(2,2-Dimethylpropionyloxy)phenylsulfonylamino]benzoyl] aminoacetic acid, competitively inhibited human neutrophil elastase (IC50=0.044 μM, Ki = 0.2μM). 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 100μM. In in vivo studies, ONO-5046 suppressed lung hemorrhage in hamster (ID50 = 82 μg/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.
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: Sivelestat was safe and well tolerated with appropriate pharmacokinetic parameters, which provided support for more diverse dosing regimen in clinical application.
: www.chinadrugtrials.org.cn identifier is CTR20210072.
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Identification and characterization of aptameric inhibitors of human neutrophil elastase
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Widespread microbial utilization of ribosomal β-amino acid-containing peptides and proteins
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