Počet záznamů: 1
Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and soluble epoxide hydrolase using pharmacophore-based virtual screening
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SYSNO ASEP 0474823 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Discovery of the first dual inhibitor of the 5-lipoxygenase-activating protein and soluble epoxide hydrolase using pharmacophore-based virtual screening Tvůrce(i) Temml, V. (AT)
Garscha, U. (DE)
Romp, E. (DE)
Schubert, G. (DE)
Gerstmeier, J. (DE)
Kutil, Zsófia (UEB-Q)
Matuszczak, B. (AT)
Waltenberger, B. (AT)
Stuppner, H. (AT)
Werz, O. (DE)
Schuster, D. (AT)Celkový počet autorů 11 Číslo článku 42751 Zdroj.dok. Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 7, FEB 20 (2017)Poč.str. 8 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova activating protein ; drug discovery ; leukotriene biosynthesis ; inflammatory diseases ; conformer generation ; arachidonic-acid ; flap ; challenges ; asthma ; risk Vědní obor RIV CE - Biochemie Obor OECD Physiology (including cytology) Institucionální podpora UEB-Q - RVO:61389030 UT WOS 000394419900001 DOI 10.1038/srep42751 Anotace Leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA) with roles in inflammatory and allergic diseases. The biosynthesis of LTs is initiated by transfer of AA via the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase (5-LO). FLAP inhibition abolishes LT formation exerting anti-inflammatory effects. The soluble epoxide hydrolase (sEH) converts AA-derived anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatetraenoic acids (diHETEs). Its inhibition consequently also counteracts inflammation. Targeting both LT biosynthesis and the conversion of EETs with a dual inhibitor of FLAP and sEH may represent a novel, powerful anti-inflammatory strategy. We present a pharmacophore-based virtual screening campaign that led to 20 hit compounds of which 4 targeted FLAP and 4 were sEH inhibitors. Among them, the first dual inhibitor for sEH and FLAP was identified, N-[4-(benzothiazol-2-ylmethoxy)-2-methylphenyl]-N'-(3,4-dichlorophenyl) urea with IC50 values of 200 nM in a cell-based FLAP test system and 20 nM for sEH activity in a cell-free assay. Pracoviště Ústav experimentální botaniky Kontakt David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Rok sběru 2018
Počet záznamů: 1