The DOI matches its Crossref record; 222 of the 224 references it cites were found in a registry or an index.
Therapeutic potential of NADPH oxidase 1/4 inhibitors
Open accessAbstract
The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation, tissue and subcellular localization and ROS products. The most studied are NOX1, 2 and 4. Genetic deletion of NOX1 and 4, in contrast to NOX2, has revealed no significant spontaneous pathologies and a pathogenic relevance of both NOX1 and 4 across multiple organs in a wide range of diseases and in particular inflammatory and fibrotic diseases. This has stimulated interest in NOX inhibitors for therapeutic application. GKT136901 and GKT137831 are two structurally related compounds demonstrating a preferential inhibition of NOX1 and 4 that have suitable properties for in vivo studies and have consequently been evaluated across a range of disease models and compared with gene deletion. In contrast to gene deletion, these inhibitors do not completely suppress ROS production, maintaining some basal level of ROS. Despite this and consistent with most gene deletion studies, these inhibitors are well tolerated and slow or prevent disease progression in a range of models of chronic inflammatory and fibrotic diseases by modulating common signal transduction pathways. Clinical trials in patients with GKT137831 have demonstrated excellent tolerability and reduction of various markers of chronic inflammation. NOX1/4 inhibition may provide a safe and effective therapeutic strategy for a range of inflammatory and fibrotic diseases. Linked Articles: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc
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“In contrast, so far no direct antioxidative side effects of GKT 137831 were reported [392] highlighting this substance as the most promising inhibitor for Nox enzymes not only in vitro but also in vivo [94,409,411,412,413,414].”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [392]
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“Both compounds inhibit Nox1, Nox4 and Nox5 and in higher concentrations also Nox2, Duox1, Duox2 [406,407,408,409], and XO [392,393,408,409].”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [392]
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- Wiesel PHL, 2012, American Society of Nephrology Kidney Week
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Metadata
- Authors
- Teixeira, G., Szyndralewiez, C., Molango, S., Carnesecchi, S., Heitz, F., Wiesel, P., & Wood, J. M.
- Affiliations
- Evotec (Germany) (DE)
- Genkyotex (Switzerland) (CH)
- Genkyotex SA Plan les Ouates Switzerland
- Inovaid Biel‐Benken Switzerland
- Corresponding author
- Wood, J M
- ORCID
- Wiesel, P
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2016-07-14
- Volume
- 174
- Issue
- 12
- Pages
- 1647-1669
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC5446584
- OpenAlex
- W2414686680
- Semantic Scholar
- 3495831cf5de9bc9c88751dc4734fc06fde77667
- Cited by
- 163
- References
- 224
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 9 · 2023: 12 · 2022: 15 · 2021: 15 · 2020: 28 · 2019: 17 · 2018: 22 · 2017: 16 · 2016: 5
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- NADPH oxidase, NOX1, NOX4, NOX2, reactive oxygen species, NADPH oxidase inhibitors, GKT137831, chronic inflammation, fibrotic diseases, redox signaling, signal transduction, oxidative stress
- MeSH terms
- NADPH Oxidase 1, NADPH Oxidase 2, Animals, Anti-Inflammatory Agents, Enzyme Inhibitors, Fibrosis, Humans, Inflammation, Pyrazoles, Pyridines, Pyridones, Pyrazolones
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