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1000 Titel
  • The Emerging Therapeutic Potential of Nitro Fatty Acids and Other Michael Acceptor-Containing Drugs for the Treatment of Inflammation and Cancer
1000 Autor/in
  1. Piesche, Matthias |
  2. Roos, Jessica |
  3. Kühn, Benjamin |
  4. Fettel, Jasmin |
  5. Hellmuth, Nadine |
  6. Brat, Camilla Anethe Sandra |
  7. Maucher, Isabelle Viktoria |
  8. Awad, Omar |
  9. Matrone, Carmela |
  10. Comerma-Steffensen, Simon |
  11. Manolikakes, Georg |
  12. Heinicke, Ulrike |
  13. Zacharowski, Kai |
  14. Steinhilber, Dieter |
  15. Maier, Thorsten Jürgen |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-09-03
1000 Erschienen in
1000 Quellenangabe
  • 11:1297
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3389/fphar.2020.01297 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495092 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Nitro fatty acids (NFAs) are endogenously generated lipid mediators deriving from reactions of unsaturated electrophilic fatty acids with reactive nitrogen species. Furthermore, Mediterranean diets can be a source of NFA. These highly electrophilic fatty acids can undergo Michael addition reaction with cysteine residues, leading to post-translational modifications (PTM) of selected regulatory proteins. Such modifications are capable of changing target protein function during cell signaling or in biosynthetic pathways. NFA target proteins include the peroxisome proliferator-activated receptor γ (PPAR-γ), the pro-inflammatory and tumorigenic nuclear factor-κB (NF-κB) signaling pathway, the pro-inflammatory 5-lipoxygenases (5-LO) biosynthesis pathway as well as soluble epoxide hydrolase (sEH), which is essentially involved in the regulation of vascular tone. In several animal models of inflammation and cancer, the therapeutic efficacy of well-tolerated NFA has been demonstrated. This has already led to clinical phase II studies investigating possible therapeutic effects of NFA in subjects with pulmonary arterial hypertension. Albeit Michael acceptors feature a broad spectrum of bioactivity, they have for a rather long time been avoided as drug candidates owing to their presumed unselective reactivity and toxicity. However, targeted covalent modification of regulatory proteins by Michael acceptors became recognized as a promising approach to drug discovery with the recent FDA approvals of the cancer therapeutics, afatanib (2013), ibrutinib (2013), and osimertinib (2015). Furthermore, the Michael acceptor, neratinib, a dual inhibitor of the human epidermal growth factor receptor 2 and epidermal growth factor receptor, was recently approved by the FDA (2017) and by the EMA (2018) for the treatment of breast cancer. Finally, a number of further Michael acceptor drug candidates are currently under clinical investigation for pharmacotherapy of inflammation and cancer. In this review, we focus on the pharmacology of NFA and other Michael acceptor drugs, summarizing their potential as an emerging class of future antiphlogistics and adjuvant in tumor therapeutics.
1000 Sacherschließung
lokal post-translational modifications
gnd 4003120-2 Arzneimittelforschung
lokal electrophilic fatty acids
lokal nitroalkylation
lokal Michael acceptor
lokal covalent drugs
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-9050-1946|https://d-nb.info/gnd/1053809271|https://d-nb.info/gnd/1173943358|https://d-nb.info/gnd/1174925086|https://d-nb.info/gnd/1243463805|https://d-nb.info/gnd/1240429835|https://d-nb.info/gnd/1136750967|https://frl.publisso.de/adhoc/uri/QXdhZCwgT21hciA=|https://orcid.org/0000-0002-6719-0107|https://orcid.org/0000-0001-6516-694X|https://orcid.org/0000-0002-4013-5757|https://orcid.org/0000-0002-0016-8124|https://orcid.org/0000-0002-0212-9110|https://orcid.org/0000-0001-8905-5208|https://orcid.org/0000-0003-3234-947X
1000 Label
1000 Förderer
  1. Else Kröner-Fresenius-Stiftung |
  2. Graduate School TRIP |
  3. Deutsche Forschungsgemeinschaft |
  4. Aarhus Universitets Forskningsfond |
1000 Fördernummer
  1. -
  2. -
  3. DFG-MA-5825/2-1; MA-5825/1-2; SFB-1039
  4. -
1000 Förderprogramm
  1. Graduate School TRIP (Translational Research Innovation-Pharma)
  2. -
  3. Heisenberg fellowship
  4. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Else Kröner-Fresenius-Stiftung |
    1000 Förderprogramm Graduate School TRIP (Translational Research Innovation-Pharma)
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer Graduate School TRIP |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm Heisenberg fellowship
    1000 Fördernummer DFG-MA-5825/2-1; MA-5825/1-2; SFB-1039
  4. 1000 joinedFunding-child
    1000 Förderer Aarhus Universitets Forskningsfond |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6432746.rdf
1000 Erstellt am 2022-03-31T13:24:29.323+0200
1000 Erstellt von 323
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1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Mon Apr 25 14:27:11 CEST 2022
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1000 Vgl. frl:6432746
1000 Oai Id
  1. oai:frl.publisso.de:frl:6432746 |
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