{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:14:41Z","timestamp":1785766481815,"version":"3.56.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,4,29]],"date-time":"2010-04-29T00:00:00Z","timestamp":1272499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>All \u03b3\u2010chain cytokines signal through JAK\u20103 and JAK\u20101 acting in tandem. We undertook this study to determine whether the JAK\u20103 selective inhibitor WYE\u2010151650 would be sufficient to disrupt cytokine signaling and to ameliorate autoimmune disease pathology without inhibiting other pathways mediated by JAK\u20101, JAK\u20102, and Tyk\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>JAK\u20103 kinase selective compounds were characterized by kinase assay and JAK\u20103\u2013dependent (interleukin\u20102 [IL\u20102]) and \u2013independent (IL\u20106, granulocyte\u2013macrophage colony\u2010stimulating factor [GM\u2010CSF]) cell\u2010based assays measuring proliferation or STAT phosphorylation. In vivo, off\u2010target signaling was measured by IL\u201022\u2013 and erythropoietin (EPO)\u2013mediated models, while on\u2010target signaling was measured by IL\u20102\u2013mediated signaling. Efficacy of JAK\u20103 inhibitors was determined using delayed\u2010type hypersensitivity (DTH) and collagen\u2010induced arthritis (CIA) models in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro, WYE\u2010151650 potently suppressed IL\u20102\u2013induced STAT\u20105 phosphorylation and cell proliferation, while exhibiting 10\u201329\u2010fold less activity against JAK\u20103\u2013independent IL\u20106\u2013 or GM\u2010CSF\u2013induced STAT phosphorylation. Ex vivo, WYE\u2010151650 suppressed IL\u20102\u2013induced STAT phosphorylation, but not IL\u20106\u2013induced STAT phosphorylation, as measured in whole blood. In vivo, WYE\u2010151650 inhibited JAK\u20103\u2013mediated IL\u20102\u2013induced interferon\u2010\u03b3 production and decreased the natural killer cell population in mice, while not affecting IL\u201022\u2013induced serum amyloid A production or EPO\u2010induced reticulocytosis. WYE\u2010151650 was efficacious in mouse DTH and CIA models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In vitro, ex vivo, and in vivo assays demonstrate that WYE\u2010151650 is efficacious in mouse CIA despite JAK\u20103 selectivity. These data question the need to broadly inhibit JAK\u20101\u2013, JAK\u20102\u2013, or Tyk\u20102\u2013dependent cytokine pathways for efficacy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27536","type":"journal-article","created":{"date-parts":[[2010,4,30]],"date-time":"2010-04-30T11:33:49Z","timestamp":1272627229000},"page":"2283-2293","source":"Crossref","is-referenced-by-count":62,"title":["Selective functional inhibition of JAK\u20103 is sufficient for efficacy in collagen\u2010induced arthritis in mice"],"prefix":"10.1002","volume":"62","author":[{"given":"Tsung H.","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hegen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Quadros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl 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