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

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

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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Crossref · 10.1016/0006-291x(91)91862-7

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13 of 13 references verified0 citation errors · 0 not checkable

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  • Inhibitor drugs targeting HNE are small non-proteinaceous synthetic molecules.

    “However, PK101 and the optimal HNE peptide substrates selected from the combinatorial library contain unnatural amino acid residues [20], and the inhibitor drugs targeting HNE are small non-proteinaceous synthetic molecules [22,23].”
  • Sulfone moieties are present in inhibitor drugs targeting HNE, including Sivelestat and BAY 85-8501.

    “This notion is consistent with the observation of sulfone moieties in inhibitor drugs targeting HNE, including Sivelestat [22] and the Bayer inhibitor, BAY 85-8501 [23].”

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Authors
Kawabata, K., Suzuki, M., Sugitani, M., Imaki, K., Toda, M., & Miyamoto, T.
Affiliations
Ono Pharmaceutical (Japan) (JP)
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
1991-06
Volume
177
Issue
2
Pages
814-820
ISSN
0006-291X (ISSN-L)
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
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 › Genetics › 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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