Karin Meirer, Daniel Glatzel, Simon Kretschmer, Sandra Kerstin Wittmann, Markus Hartmann, René Blöcher, Carlo Federico Angioni, Gerd Geisslinger, Dieter Steinhilber, Bettina Hofmann, Robert Fürst, Ewgenij Proschak
- The arachidonic acid cascade is a key player in inflammation, and numerous well-established drugs interfere with this pathway. Previous studies have suggested that simultaneous inhibition of 5-lipoxygenase (5-LO) and soluble epoxide hydrolase (sEH) results in synergistic anti-inflammatory effects. In this study, a novel prototype of a dual 5-LO/sEH inhibitor KM55 was rationally designed and synthesized. KM55 was evaluated in enzyme activity assays with recombinant enzymes. Furthermore, activity of KM55 in human whole blood and endothelial cells was investigated. KM55 potently inhibited both enzymes in vitro and attenuated the formation of leukotrienes in human whole blood. KM55 was also tested in a cell function-based assay. The compound significantly inhibited the LPS-induced adhesion of leukocytes to endothelial cells by blocking leukocyte activation.
Metadaten| Author: | Karin Meirer, Daniel Glatzel, Simon Kretschmer, Sandra Kerstin Wittmann, Markus Hartmann, René Blöcher, Carlo Federico AngioniORCiD, Gerd GeisslingerORCiDGND, Dieter SteinhilberORCiDGND, Bettina Hofmann, Robert FürstORCiDGND, Ewgenij ProschakORCiDGND |
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| URN: | urn:nbn:de:hebis:30:3-436919 |
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| DOI: | https://doi.org/10.3390/molecules22010045 |
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| ISSN: | 1420-3049 |
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| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28036068 |
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| Parent Title (English): | Molecules |
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| Publisher: | Molecular Diversity Preservation International |
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| Place of publication: | Basel |
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| Contributor(s): | Cornelis J. van der Schyf |
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| Document Type: | Article |
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| Language: | English |
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| Date of Publication (online): | 2017/06/12 |
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| Year of first Publication: | 2016 |
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| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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| Release Date: | 2017/06/12 |
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| Tag: | 5-lipoxygenase; designed multitarget ligands; inflammation; leukocyte-endothelial cell interaction; soluble epoxide hydrolase |
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| Volume: | 22 |
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| Issue: | 1, Art. 45 |
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| Page Number: | 10 |
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| First Page: | 1 |
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| Last Page: | 10 |
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| Note: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0). |
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| HeBIS-PPN: | 425326144 |
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| Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
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| Biochemie, Chemie und Pharmazie / Pharmazie |
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| Biowissenschaften / Biowissenschaften |
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| Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
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| 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
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| Sammlungen: | Universitätspublikationen |
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| Licence (German): |  Creative Commons - Namensnennung 4.0 |
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Creative Commons - Namensnennung 4.0