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To address this hypothesis, we synthesized selective indole\u2010based OXE receptor antagonists. Because rodents lack an OXE receptor orthologue, we sought to determine whether these antagonists could attenuate allergen\u2010induced skin eosinophilia in sensitized monkeys.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>In a pilot study, cynomolgus monkeys with environmentally acquired sensitivity to <jats:italic>Ascaris suum<\/jats:italic> were treated orally with the \u201cfirst\u2010generation\u201d OXE antagonist <jats:bold>230<\/jats:bold> prior to intradermal injection of 5\u2010oxo\u2010ETE or <jats:italic>Ascaris<\/jats:italic> extract. Eosinophils were evaluated in punch biopsy samples taken 6 or 24\u00a0hr later. We subsequently treated captive\u2010bred rhesus monkeys sensitized to house dust mite (HDM) allergen with a more recently developed OXE antagonist, <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold>, and evaluated its effects on dermal eosinophilia induced by either 5\u2010oxo\u2010ETE or HDM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In a pilot experiment, both 5\u2010oxo\u2010ETE and <jats:italic>Ascaris<\/jats:italic> extract induced dermal eosinophilia in cynomolgus monkeys, which appeared to be reduced by <jats:bold>230<\/jats:bold>. Subsequently, we found that the related OXE antagonist <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold> is a highly potent inhibitor of 5\u2010oxo\u2010ETE\u2010induced activation of rhesus monkey eosinophils in vitro and has a half\u2010life in plasma of about 6\u00a0hr after oral administration. <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold> significantly inhibited eosinophil infiltration into the skin in response to both intradermally administered 5\u2010oxo\u2010ETE and HDM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>5\u2010Oxo\u2010ETE may play an important role in allergen\u2010induced eosinophilia. Blocking its effects with <jats:bold><jats:italic>S<\/jats:italic>\u2010Y048<\/jats:bold> may provide a novel therapeutic approach for eosinophilic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14872","type":"journal-article","created":{"date-parts":[[2019,10,26]],"date-time":"2019-10-26T19:09:37Z","timestamp":1572116977000},"page":"360-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of allergen\u2010induced dermal eosinophilia by an oxoeicosanoid receptor antagonist in non\u2010human primates"],"prefix":"10.1111","volume":"177","author":[{"given":"Lisa A.","family":"Miller","sequence":"first","affiliation":[{"name":"California National Primate Research Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Cossette","sequence":"additional","affiliation":[{"name":"Meakins\u2010Christie Laboratories, Centre for Translational Biology McGill University Health Centre  Montreal, Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shishir","family":"Chourey","sequence":"additional","affiliation":[{"name":"Claude Pepper Institute and Department of Chemistry Florida Institute of Technology  Melbourne Florida USA"},{"name":"Department of Chemical Development Albany Molecular Research Inc.  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