{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T22:16:41Z","timestamp":1775254601282,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,1,4]],"date-time":"2019-01-04T00:00:00Z","timestamp":1546560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Prostanoid EP\n                      <jats:sub>2<\/jats:sub>\n                      receptor agonists exhibit several activities including ocular hypotension, tocolysis and anti\u2010inflammatory activity. This report describes the affinity and selectivity of a structurally novel, non\u2010prostanoid EP\n                      <jats:sub>2<\/jats:sub>\n                      receptor agonist, PGN\u20109856, and its therapeutic potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      The pharmacology of a series of non\u2010prostanoid EP\n                      <jats:sub>2<\/jats:sub>\n                      receptor agonists was determined according to functional and radioligand binding studies, mostly using human recombinant prostanoid receptor transfectants. The selectivity of PGN\u20109856, as the preferred compound, was subsequently determined by using a diverse variety of non\u2010prostanoid target proteins. The therapeutic potential of PGN\u20109856 was addressed by determining its activity in relevant primate cell, tissue and disease models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      PGN\u20109856 was a selective and high affinity (pKi\u00a0\u2265\u00a08.3) ligand at human recombinant EP\n                      <jats:sub>2<\/jats:sub>\n                      receptors. In addition to high affinity binding, it was a potent and full EP\n                      <jats:sub>2<\/jats:sub>\n                      receptor agonist with a high level of selectivity at EP\n                      <jats:sub>1<\/jats:sub>\n                      , EP\n                      <jats:sub>3<\/jats:sub>\n                      , EP\n                      <jats:sub>4<\/jats:sub>\n                      , DP, FP, IP and TP receptors. In cells overexpressing human recombinant EP\n                      <jats:sub>2<\/jats:sub>\n                      receptors, PGN\u20109856 displayed a potency (pEC\n                      <jats:sub>50<\/jats:sub>\n                      \u2265\u00a08.5) and a maximal response (increase in cAMP) comparable to that of the endogenous agonist PGE\n                      <jats:sub>2<\/jats:sub>\n                      . PGN\u20109856 exhibited no appreciable affinity (up 10\u00a0\u03bcM) for a range of 53 other receptors, ion channels and enzymes. Finally, PGN\u20109856 exhibited tocolytic, anti\u2010inflammatory and long\u2010acting ocular hypotensive properties consistent with its potent EP\n                      <jats:sub>2<\/jats:sub>\n                      receptor agonist properties.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      PGN\u20109856 is a potent, selective and efficacious prostanoid EP\n                      <jats:sub>2<\/jats:sub>\n                      receptor agonist with diverse potential therapeutic applications: tocolytic, anti\u2010inflammatory and notably anti\u2010glaucoma.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.14525","type":"journal-article","created":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T04:08:26Z","timestamp":1540008506000},"page":"687-698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The affinity, intrinsic activity and selectivity of a structurally novel EP\n                    <sub>2<\/sub>\n                    receptor agonist at human prostanoid receptors"],"prefix":"10.1111","volume":"176","author":[{"given":"R A","family":"Coleman","sequence":"first","affiliation":[{"name":"Asterand Bioscience Royston UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A J","family":"Woodrooffe","sequence":"additional","affiliation":[{"name":"Asterand Bioscience Royston UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K L","family":"Clark","sequence":"additional","affiliation":[{"name":"Asterand Bioscience Royston UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C B","family":"Toris","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center Omaha NE USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Fan","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center Omaha NE USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J W","family":"Wang","sequence":"additional","affiliation":[{"name":"JeniVision Inc. 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