{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:53:27Z","timestamp":1792403607955,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,5,27]],"date-time":"2014-05-27T00:00:00Z","timestamp":1401148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,6]]},"abstract":"Background and Purpose<\/jats:title>Leukotrienes (LT<\/jats:styled-content>s) are inflammatory mediators produced via the 5\u2010lipoxygenase (5\u2010LOX<\/jats:styled-content>) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivativeBRP<\/jats:styled-content>\u20107 as chemotype for anti\u2010LT<\/jats:styled-content>agents by virtual screening targeting 5\u2010LOX<\/jats:styled-content>\u2010activating protein (FLAP<\/jats:styled-content>). Here, we aimed to reveal thein vitro<\/jats:italic>andin vivo<\/jats:italic>pharmacology ofBRP<\/jats:styled-content>\u20107 as an inhibitor ofLT<\/jats:styled-content>biosynthesis.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>We analysedLT<\/jats:styled-content>formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB<\/jats:styled-content>) and in cell\u2010free assays. The effectiveness ofBRP<\/jats:styled-content>\u20107in vivo<\/jats:italic>was evaluated in rat carrageenan\u2010induced pleurisy and mouse zymosan\u2010induced peritonitis.<\/jats:p><\/jats:sec>Key Results<\/jats:title>BRP<\/jats:styled-content>\u20107 potently suppressedLT<\/jats:styled-content>formation in neutrophils and monocytes and this was accompanied by impaired 5\u2010LOX<\/jats:styled-content>co\u2010localization withFLAP<\/jats:styled-content>. Neither the cellular viability nor the activity of 5\u2010LOX<\/jats:styled-content>in cell\u2010free assays was affected byBRP<\/jats:styled-content>\u20107, indicating that a functionalFLAP<\/jats:styled-content>is needed forBRP<\/jats:styled-content>\u20107 to inhibit LTs, andFLAP<\/jats:styled-content>bound toBRP<\/jats:styled-content>\u20107 linked to a solid matrix. Compared with theFLAP<\/jats:styled-content>inhibitorMK<\/jats:styled-content>\u2010886,BRP<\/jats:styled-content>\u20107 did not significantly inhibitCOX<\/jats:styled-content>\u20101 or microsomal prostaglandinE<\/jats:styled-content>2<\/jats:sub>synthase\u20101, implying the selectivity ofBRP<\/jats:styled-content>\u20107 forFLAP<\/jats:styled-content>. Finally,BRP<\/jats:styled-content>\u20107 was effective inHWB<\/jats:styled-content>and impaired inflammationin vivo<\/jats:italic>, in rat pleurisy and mouse peritonitis, along with reducingLT<\/jats:styled-content>levels.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>BRP<\/jats:styled-content>\u20107 potently suppressesLT<\/jats:styled-content>biosynthesis by interacting withFLAP<\/jats:styled-content>and exhibits anti\u2010inflammatory effectivenessin vivo<\/jats:italic>, with promising potential for further development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12625","type":"journal-article","created":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T12:24:31Z","timestamp":1392207871000},"page":"3051-3064","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["The novel benzimidazole derivativeBRP<\/scp>\u20107 inhibits leukotriene biosynthesisin vitro<\/i>andin vivo<\/i>by targeting 5\u2010lipoxygenase\u2010activating protein (FLAP<\/scp>)"],"prefix":"10.1111","volume":"171","author":[{"given":"C","family":"Pergola","sequence":"first","affiliation":[{"name":"Institute of Pharmacy Friedrich\u2010Schiller\u2010University Jena Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Gerstmeier","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy Friedrich\u2010Schiller\u2010University Jena Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"M\u00f6nch","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy Friedrich\u2010Schiller\u2010University Jena Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"\u00c7al\u0131\u015fkan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Faculty of Pharmacy Gazi University Ankara 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