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Screens of 292,000 compounds identified 93 that at 20 \u03bcM (\n            <jats:italic>i<\/jats:italic>\n            ) potentiated the cAMP response to a low concentration of PGE\n            <jats:sub>2<\/jats:sub>\n            by &gt; 50%; (\n            <jats:italic>ii<\/jats:italic>\n            ) had no effect on EP4 or \u03b22 adrenergic receptors, the cAMP assay itself, or the parent cell line; and (\n            <jats:italic>iii<\/jats:italic>\n            ) increased the potency of PGE\n            <jats:sub>2<\/jats:sub>\n            on EP2 receptors at least 3-fold. In aqueous solution, the active compounds are largely present as nanoparticles that appear to serve as active reservoirs for bioactive monomer. From 94 compounds synthesized or purchased, based on the modification of one hit compound, the most active increased the potency of PGE\n            <jats:sub>2<\/jats:sub>\n            on EP2 receptors 4- to 5-fold at 10 to 20 \u03bcM and showed substantial neuroprotection in an excitotoxicity model. These small molecules represent previously undescribed allosteric modulators of a PGE\n            <jats:sub>2<\/jats:sub>\n            receptor. Our results strongly reinforce the notion that activation of EP2 receptors by endogenous PGE\n            <jats:sub>2<\/jats:sub>\n            released in a cell-injury setting is neuroprotective.\n          <\/jats:p>","DOI":"10.1073\/pnas.0909310107","type":"journal-article","created":{"date-parts":[[2010,1,15]],"date-time":"2010-01-15T02:09:56Z","timestamp":1263521396000},"page":"2307-2312","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["Neuroprotection by selective allosteric potentiators of the EP2 prostaglandin receptor"],"prefix":"10.1073","volume":"107","author":[{"given":"Jianxiong","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Pharmacology,"}]},{"given":"Thota","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Department of Chemistry,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]},{"given":"Yuhong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]},{"given":"Pahk","family":"Thepchatri","sequence":"additional","affiliation":[{"name":"Department of Chemistry,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]},{"given":"Asheebo","family":"Rojas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,"}]},{"given":"Iestyn","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]},{"given":"Serdar","family":"Kurtkaya","sequence":"additional","affiliation":[{"name":"Department of Chemistry,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]},{"given":"Lian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]},{"given":"Min","family":"Qui","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]},{"given":"Geidy","family":"Serrano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,"}]},{"given":"Renee","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,"}]},{"given":"Aiming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Chemistry,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]},{"given":"Ray","family":"Dingledine","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,"},{"name":"Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA 30322"}]}],"member":"341","published-online":{"date-parts":[[2010,1,14]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1073\/pnas.93.6.2317","article-title":"COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex","volume":"93","author":"Kaufmann WE","year":"1996","unstructured":"WE Kaufmann, PF Worley, J Pegg, M Bremer, P Isakson, COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. 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