{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T01:55:40Z","timestamp":1770688540024,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,25]],"date-time":"2013-02-25T00:00:00Z","timestamp":1361750400000},"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":[[2013,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The efficacy of <jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125, a small\u2010molecule SH2\u2010containing inositol\u20105\u2032\u2010phosphatase 1 (<jats:styled-content style=\"fixed-case\">SHIP1<\/jats:styled-content>) activator and clinical development candidate, is investigated in rodent models of inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125 was administered orally in a mouse model of passive cutaneous anaphylaxis (<jats:styled-content style=\"fixed-case\">PCA<\/jats:styled-content>) and a number of rodent models of respiratory inflammation including: cigarette smoke, <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> and ovalbumin (<jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content>)\u2010mediated airway inflammation. <jats:styled-content style=\"fixed-case\">SHIP1<\/jats:styled-content> dependency of the <jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125 mechanism of action was investigated by comparing the efficacy in wild\u2010type and SHIP1\u2010deficient mice subjected to an intrapulmonary <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125 exerted anti\u2010inflammatory effects in all of the models studied. <jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125 decreased the <jats:styled-content style=\"fixed-case\">PCA<\/jats:styled-content> response at all doses tested. Using bronchoalveolar lavage (<jats:styled-content style=\"fixed-case\">BAL<\/jats:styled-content>) cell counts as an end point, oral or aerosolized <jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125 dose dependently decreased the <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010mediated pulmonary neutrophilic infiltration at 3\u201330\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> and 0.15\u201315\u2009\u03bcg\u2009kg<jats:sup>\u22121<\/jats:sup> respectively. <jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125 suppressed the <jats:styled-content style=\"fixed-case\">OVA<\/jats:styled-content>\u2010mediated airway inflammation at 0.1\u201310\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>. In the smoke\u2010induced airway inflammation model, <jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125 was tested at 30\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup> and significantly reduced the neutrophil infiltration of the <jats:styled-content style=\"fixed-case\">BAL<\/jats:styled-content> fluid. <jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125 (10\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>) decreased <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced pulmonary neutrophilia in wild\u2010type mice but not in <jats:styled-content style=\"fixed-case\">SHIP1<\/jats:styled-content>\u2010deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">SHIP1<\/jats:styled-content> activator, <jats:styled-content style=\"fixed-case\">AQX<\/jats:styled-content>\u20101125, suppresses leukocyte accumulation and inflammatory mediator release in rodent models of pulmonary inflammation and allergy. As shown in the mouse model of <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced lung inflammation, the efficacy of the compound is dependent on the presence of <jats:styled-content style=\"fixed-case\">SHIP1<\/jats:styled-content>. Pharmacological <jats:styled-content style=\"fixed-case\">SHIP1<\/jats:styled-content> activation may have clinical potential for the treatment of pulmonary inflammatory diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Article<\/jats:title><jats:p>This article is accompanied by Stenton <jats:italic>et\u2009al<\/jats:italic>., pp. 1506\u20131518 of this issue. To view this article visit http:\/\/dx.doi.org\/<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.12039\/abstract\">10.1111\/bph.12039<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12038","type":"journal-article","created":{"date-parts":[[2012,11,2]],"date-time":"2012-11-02T08:06:49Z","timestamp":1351843609000},"page":"1519-1529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Characterization of <scp>AQX<\/scp>\u20101125, a small\u2010molecule <scp>SHIP1<\/scp> activator"],"prefix":"10.1111","volume":"168","author":[{"given":"Grant R","family":"Stenton","sequence":"first","affiliation":[{"name":"Aquinox Pharmaceuticals Inc.  Richmond BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lloyd F","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Aquinox Pharmaceuticals Inc.  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