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  1. Artikel: NF-κB Signaling and Inflammation—Drug Repurposing to Treat Inflammatory Disorders?

    Roberti, Annabell / Chaffey, Laura Elizabeth / Greaves, David R.

    Biology. 2022 Feb. 26, v. 11, no. 3

    2022  

    Abstract: NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB ...

    Abstract NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and have proven to be controversial. Drug repurposing strategies are a promising alternative to de novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs.
    Schlagwörter COVID-19 infection ; DNA damage ; Severe acute respiratory syndrome coronavirus 2 ; autoimmunity ; drug development ; health services ; humans ; inflammation ; lungs ; oxidative stress ; pandemic ; pneumonia ; rheumatoid arthritis ; risk reduction ; sclerosis
    Sprache Englisch
    Erscheinungsverlauf 2022-0226
    Erscheinungsort Multidisciplinary Digital Publishing Institute
    Dokumenttyp Artikel
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology11030372
    Datenquelle NAL Katalog (AGRICOLA)

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  2. Artikel: NF-κB Signaling and Inflammation-Drug Repurposing to Treat Inflammatory Disorders?

    Roberti, Annabell / Chaffey, Laura Elizabeth / Greaves, David R

    Biology

    2022  Band 11, Heft 3

    Abstract: NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB ...

    Abstract NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and have proven to be controversial. Drug repurposing strategies are a promising alternative to de novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs.
    Sprache Englisch
    Erscheinungsdatum 2022-02-26
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology11030372
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Drug repurposing in cardiovascular inflammation: Successes, failures, and future opportunities.

    Chaffey, Laura / Roberti, Annabell / Greaves, David R

    Frontiers in pharmacology

    2022  Band 13, Seite(n) 1046406

    Abstract: Drug repurposing is an attractive, pragmatic approach to drug discovery that has yielded success across medical fields over the years. The use of existing medicines for novel indications enables dramatically reduced development costs and timescales ... ...

    Abstract Drug repurposing is an attractive, pragmatic approach to drug discovery that has yielded success across medical fields over the years. The use of existing medicines for novel indications enables dramatically reduced development costs and timescales compared with
    Sprache Englisch
    Erscheinungsdatum 2022-10-21
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.1046406
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  4. Artikel ; Online: Drug repurposing screen identifies novel anti-inflammatory activity of sunitinib in macrophages.

    Chaffey, Laura E / Roberti, Annabell / Bowman, Amelia / O'Brien, Conan Jo / Som, Liliana / Purvis, Gareth Sd / Greaves, David R

    European journal of pharmacology

    2024  Band 969, Seite(n) 176437

    Abstract: Inflammation is a driver of human disease and an unmet clinical need exists for new anti-inflammatory medicines. As a key cell type in both acute and chronic inflammatory pathologies, macrophages are an appealing therapeutic target for anti-inflammatory ... ...

    Abstract Inflammation is a driver of human disease and an unmet clinical need exists for new anti-inflammatory medicines. As a key cell type in both acute and chronic inflammatory pathologies, macrophages are an appealing therapeutic target for anti-inflammatory medicines. Drug repurposing - the use of existing medicines for novel indications - is an attractive strategy for the identification of new anti-inflammatory medicines with reduced development costs and lower failure rates than de novo drug discovery. In this study, FDA-approved medicines were screened in a murine macrophage NF-κB reporter cell line to identify potential anti-inflammatory drug repurposing candidates. The multi-tyrosine kinase inhibitor sunitinib was found to be a potent inhibitor of NF-κB activity and suppressor of inflammatory mediator production in murine bone marrow derived macrophages. Furthermore, oral treatment with sunitinib in mice was found to reduce TNFα production, inflammatory gene expression and organ damage in a model of endotoxemia via inhibition of NF-κB. Finally, we revealed sunitinib to have immunomodulatory effects in a model of chronic cardiovascular inflammation by reducing circulating TNFα. This study validates drug repurposing as a strategy for the identification of novel anti-inflammatory medicines and highlights sunitinib as a potential drug repurposing candidate for inflammatory disease via inhibition of NF-κB signalling.
    Mesh-Begriff(e) Humans ; Mice ; Animals ; NF-kappa B/metabolism ; Sunitinib/pharmacology ; Tumor Necrosis Factor-alpha/metabolism ; Drug Repositioning ; Macrophages ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Anti-Inflammatory Agents/metabolism ; Inflammation/metabolism ; Lipopolysaccharides/pharmacology ; Lipopolysaccharides/metabolism
    Chemische Substanzen NF-kappa B ; Sunitinib (V99T50803M) ; Tumor Necrosis Factor-alpha ; Anti-Inflammatory Agents ; Lipopolysaccharides
    Sprache Englisch
    Erscheinungsdatum 2024-02-28
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2024.176437
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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