{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:55:21Z","timestamp":1792194921228,"version":"4.4.0"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2011,11,15]],"date-time":"2011-11-15T00:00:00Z","timestamp":1321315200000},"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":[[2011,12]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>Studies of the role of the prostaglandin EP<jats:sub>2<\/jats:sub>receptor) have been limited by the availability of potent and selective antagonist tools. Here we describe the<jats:italic>in vitro<\/jats:italic>\/<jats:italic>in vivo<\/jats:italic>pharmacological characterization of a novel EP<jats:sub>2<\/jats:sub>receptor antagonist, PF\u201004418948 (1\u2010(4\u2010fluorobenzoyl)\u20103\u2010{[(6\u2010methoxy\u20102\u2010naphthyl)oxy]methyl} azetidine\u20103\u2010carboxylic acid).<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>Functional antagonist potency was assessed in cell\u2010based systems expressing human EP<jats:sub>2<\/jats:sub>receptors and native tissue preparations from human, dog and mouse. The selectivity of PF\u201004418948 was assessed against related receptors and a panel of GPCRs, ion channels and enzymes. The ability of PF\u201004418948 to pharmacologically block EP<jats:sub>2<\/jats:sub>receptor function<jats:italic>in vivo<\/jats:italic>was tested in rats.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>PF\u201004418948 inhibited prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>)\u2010induced increase in cAMP in cells expressing EP<jats:sub>2<\/jats:sub>receptors with a functional K<jats:sub>B<\/jats:sub>value of 1.8\u2003nM. In human myometrium, PF\u201004418948 produced a parallel, rightward shift of the butaprost\u2010induced inhibition of the contractions induced by electrical field stimulation with an apparent K<jats:sub>B<\/jats:sub>of 5.4\u2003nM. In dog bronchiole and mouse trachea, PF\u201004418948 produced parallel rightward shifts of the PGE<jats:sub>2<\/jats:sub>\u2010induced relaxation curve with a K<jats:sub>B<\/jats:sub>of 2.5\u2003nM and an apparent K<jats:sub>B<\/jats:sub>of 1.3\u2003nM respectively. Reversal of the PGE<jats:sub>2<\/jats:sub>\u2010induced relaxation in the mouse trachea by PF\u201004418948 produced an IC<jats:sub>50<\/jats:sub>value of 2.7\u2003nM. Given orally, PF\u201004418948 attenuated the butaprost\u2010induced cutaneous blood flow response in rats. PF\u201004418948 was selective for EP<jats:sub>2<\/jats:sub>receptors over homologous and unrelated receptors, enzymes and channels.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>PF\u201004418948 is an orally active, potent and selective surmountable EP<jats:sub>2<\/jats:sub>receptor antagonist that should aid further elaboration of EP<jats:sub>2<\/jats:sub>receptor function.<\/jats:p><jats:p><jats:bold>LINKED ARTICLE<\/jats:bold>This article is commented on by Birrell and Nials, pp. 1845\u20131846 of this issue. To view this commentary visit<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/j.1476-5381.2011.01494.x\">http:\/\/dx.doi.org\/10.1111\/j.1476\u20105381.2011.01494.x<\/jats:ext-link><\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01495.x","type":"journal-article","created":{"date-parts":[[2011,5,19]],"date-time":"2011-05-19T11:59:26Z","timestamp":1305806366000},"page":"1847-1856","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["<i>In vitro<\/i>and<i>in vivo<\/i>characterization of PF\u201004418948, a novel, potent and selective prostaglandin EP<sub>2<\/sub>receptor antagonist"],"prefix":"10.1111","volume":"164","author":[{"given":"KJ","family":"af 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