TY  - JOUR
A1  - Meirer, Karin
A1  - Glatzel, Daniel
A1  - Kretschmer, Simon
A1  - Wittmann, Sandra Kerstin
A1  - Hartmann, Markus
A1  - Blöcher, René
A1  - Angioni, Carlo Federico
A1  - Geisslinger, Gerd
A1  - Steinhilber, Dieter
A1  - Hofmann, Bettina
A1  - Fürst, Robert
A1  - Proschak, Ewgenij
T1  - Design, synthesis and cellular characterization of a dual inhibitor of 5-lipoxygenase and soluble epoxide hydrolase
T2  - Molecules
N2  - 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.
KW  - soluble epoxide hydrolase
KW  - 5-lipoxygenase
KW  - inflammation
KW  - designed multitarget ligands
KW  - leukocyte-endothelial cell interaction
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/43691
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-436919
SN  - 1420-3049
N1  - 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).
VL  - 22
IS  - 1, Art. 45
SP  - 1
EP  - 10
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -