{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:52:27Z","timestamp":1787496747474,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,6,21]],"date-time":"2013-06-21T00:00:00Z","timestamp":1371772800000},"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":[[2013,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Glucocorticoids are highly effective therapies for a range of inflammatory diseases. Advances in the understanding of the diverse molecular mechanisms underpinning glucocorticoid action suggest that anti\u2010inflammatory molecules with reduced side effect liabilities can be discovered. Here we set out to explore whether modification of the 17\u03b1 position of the steroid nucleus could generate molecules with a unique pharmacological profile and to determine whether such molecules would retain anti\u2010inflammatory activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The pharmacological properties of\n                      <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>\n                      870086 were compared with fluticasone propionate (\n                      <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content>\n                      ) using a range of cellular and\n                      <jats:italic>in vivo<\/jats:italic>\n                      model systems, including extensive gene expression profiling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>\n                      870086 repressed inflammatory cytokine release from lung epithelial cells in a similar manner to\n                      <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content>\n                      but antagonized the effect of dexamethasone on\n                      <jats:styled-content style=\"fixed-case\">MMTV<\/jats:styled-content>\n                      \u2010driven reporter gene transactivation.\n                      <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>\n                      870086 had a strong effect on the expression of some glucocorticoid\u2010regulated genes (such as\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">PTGS2<\/jats:styled-content>\n                      <\/jats:italic>\n                      ), while having minimal impact on the expression of other known target genes (such as\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">SGK<\/jats:styled-content>\n                      <\/jats:italic>\n                      ).\n                      <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>\n                      870086 retained the ability to strengthen tight junctions in epithelial cell culture but, unlike\n                      <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content>\n                      , was unable to protect the culture from elastase\u2010mediated damage. In murine models of irritant\u2010induced contact dermatitis and ovalbumin\u2010induced allergic inflammation,\n                      <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>\n                      870086 showed comparable anti\u2010inflammatory efficacy to\n                      <jats:styled-content style=\"fixed-case\">FP<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>\n                      870086 is a potent anti\u2010inflammatory compound with a unique ability to regulate only a subset of those genes that are normally affected by classical glucocorticoids. It has the potential to become a new topical steroid with a different safety profile to existing therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.12232","type":"journal-article","created":{"date-parts":[[2013,5,3]],"date-time":"2013-05-03T06:23:21Z","timestamp":1367562201000},"page":"1389-1403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Discovery of\n                    <scp>GW<\/scp>\n                    870086: a potent anti\u2010inflammatory steroid with a unique pharmacological profile"],"prefix":"10.1111","volume":"169","author":[{"given":"I J","family":"Uings","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Stevenage Herts UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Needham","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Stevenage Herts 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