Unknown

Dataset Information

0

Design, Synthesis and Cellular Characterization of a Dual Inhibitor of 5-Lipoxygenase and Soluble Epoxide Hydrolase.

ABSTRACT: 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.

SUBMITTER: Meirer K 

PROVIDER: S-EPMC6155600 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Design, Synthesis and Cellular Characterization of a Dual Inhibitor of 5-Lipoxygenase and Soluble Epoxide Hydrolase.

Meirer Karin K   Glatzel Daniel D   Kretschmer Simon S   Wittmann Sandra K SK   Hartmann Markus M   Blöcher René R   Angioni Carlo C   Geisslinger Gerd G   Steinhilber Dieter D   Hofmann Bettina B   Fürst Robert R   Proschak Ewgenij E  

Molecules (Basel, Switzerland) 20161229 1

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 <b>KM55</b> was rationally designed and synthesized. <b>KM55</b> was evaluated in enzyme activity assays with recombinant enzymes. Furtherm  ...[more]

Similar Datasets

Unknown Design, Synthesis, and Pharmacological Characterization of a Potent Soluble Epoxide Hydrolase Inhibitor for the Treatment of Acute Pancreatitis.
| S-EPMC10350924 | biostudies-literature
Unknown Design and Potency of Dual Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase Inhibitors.
| S-EPMC6210075 | biostudies-literature
Unknown Design of Dual Inhibitors of Soluble Epoxide Hydrolase and LTA<sub>4</sub> Hydrolase.
| S-EPMC7073873 | biostudies-literature
Unknown Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and soluble epoxide hydrolase using pharmacophore-based virtual screening.
| S-EPMC5317001 | biostudies-literature
Unknown Orally Available Soluble Epoxide Hydrolase/Phosphodiesterase 4 Dual Inhibitor Treats Inflammatory Pain.
| S-EPMC5933862 | biostudies-literature
Unknown Computer-Aided Fragment Growing Strategies to Design Dual Inhibitors of Soluble Epoxide Hydrolase and LTA4 Hydrolase.
| S-EPMC7294724 | biostudies-literature
Unknown Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase.
| S-EPMC5571211 | biostudies-other
Unknown Dual Farnesoid X Receptor/Soluble Epoxide Hydrolase Modulators Derived from Zafirlukast.
| S-EPMC7004070 | biostudies-literature
Unknown Inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model.
| S-EPMC3285377 | biostudies-literature
Unknown Design, synthesis and biological evaluation of 4-benzamidobenzoic Acid hydrazide derivatives as novel soluble epoxide hydrolase inhibitors.
| S-EPMC3977053 | biostudies-literature