Cited by 370Protease and Inhibitor MechanismsNeutrophil, Myeloperoxidase and Oxidative MechanismsCoagulation, Bradykinin, Polyphosphates, and Angioedema

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ONO-5046, a novel inhibitor of human neutrophil elastase

Kawabata, Kazuhito, Suzuki, Mayumi, Sugitani, Masafumi, Imaki, Katsuhiro, Toda, Masaaki, Miyamoto, Tsumoru·1991·Biochemical and Biophysical Research Communications

DOI 10.1016/0006-291x(91)91862-7

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Abstract

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.

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Authors: Kawabata, K., Suzuki, M., Sugitani, M., Imaki, K., Toda, M., & Miyamoto, T.
Affiliations: Ono Pharmaceutical (Japan) (JP)
ORCID: Suzuki, Mayumi
Venue: Biochemical and Biophysical Research Communications
Publisher: Elsevier BV
Published: 1991-06
Volume: 177
Issue: 2
Pages: 814-820
ISSN: 0006-291X (ISSN-L)
DOI: 10.1016/0006-291x(91)91862-7
OpenAlex: W2039697569
Cited by: 359
References: 13
Citations by year: 2026: 8 · 2025: 6 · 2024: 11 · 2023: 10 · 2022: 10 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 18 · 2014: 8 · 2013: 11 · 2012: 12
FWCI: 2.09
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochemical and Biophysical Research Communications (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Health Sciences › Medicine › Hematology › Coagulation, Bradykinin, Polyphosphates, and Angioedema
Keywords: ONO-5046, human neutrophil elastase, leukocyte elastase, elastase inhibitors, competitive inhibition, serine protease inhibition, pulmonary hemorrhage
MeSH terms: Animals, Binding, Competitive, Capillary Permeability, Glycine, Guinea Pigs, Cricetinae, Hemorrhage, Humans, Lung Diseases, Male, Mesocricetus, Neutrophils, Pancreatic Elastase, Rabbits, Skin Diseases, Sulfonamides, Mice, Rats

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ONO-5046, a novel inhibitor of human neutrophil elastase

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