{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T13:45:29Z","timestamp":1776001529866,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,3,26]],"date-time":"2015-03-26T00:00:00Z","timestamp":1427328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation, Republic of Korea","doi-asserted-by":"crossref","award":["2011-0019397"],"award-info":[{"award-number":["2011-0019397"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"Background and Purpose<\/jats:title>Blockade of the actions of urotensin\u2010II<\/jats:styled-content> (U<\/jats:styled-content>\u2010II<\/jats:styled-content>) mediated by the urotensin (UT<\/jats:styled-content>) receptor should improve cardiac function and prevent cardiac remodelling in cardiovascular disease. Here, we have evaluated the pharmacological properties of the recently identified UT<\/jats:styled-content> receptor antagonist, 2\u2010(6,7\u2010dichloro\u20103\u2010oxo\u20102H<\/jats:styled-content>\u2010benzo[b][1,4]oxazin\u20104(3H<\/jats:styled-content>)\u2010yl)\u2010N<\/jats:styled-content>\u2010methyl\u2010N<\/jats:styled-content>\u2010(2\u2010(pyrrolidin\u20101\u2010yl)\u20101\u2010(4\u2010(thiophen\u20103\u2010yl)phenyl) ethyl)acetamide (KR<\/jats:styled-content>36676).<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Pharmacological properties of KR<\/jats:styled-content>36676 were studied in a range of in vitro<\/jats:italic> assays (receptor binding, calcium mobilization, stress fibre formation, cellular hypertrophy) and in vivo<\/jats:italic> animal models such as cardiac hypertrophy induced by transverse aortic constriction (TAC<\/jats:styled-content>) or myocardial infarction (MI<\/jats:styled-content>).<\/jats:p><\/jats:sec>Key Results<\/jats:title>KR<\/jats:styled-content>36676 displayed high binding affinity for the UT<\/jats:styled-content> receptor (K<\/jats:italic><\/jats:styled-content>i<\/jats:sub>: 0.7\u2009nM), similar to that of U<\/jats:styled-content>\u2010II<\/jats:styled-content> (0.4\u2009nM), and was a potent antagonist at that receptor (IC<\/jats:styled-content>50<\/jats:sub>: 4.0\u2009nM). U<\/jats:styled-content>\u2010II<\/jats:styled-content>\u2010induced stress fibre formation and cellular hypertrophy were significantly inhibited with low concentrations of KR<\/jats:styled-content>36676 (\u22650.01\u2009\u03bcM). Oral administration of KR<\/jats:styled-content>36676 (30\u2009mg\u00b7kg\u22121<\/jats:sup>) in a TAC<\/jats:styled-content> model in mice attenuated cardiac hypertrophy and myocardial fibrosis. Moreover, KR<\/jats:styled-content>36676 restored cardiac function and myocyte size in rats with MI<\/jats:styled-content>\u2010induced cardiac hypertrophy.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>A highly potent UT<\/jats:styled-content> receptor antagonist exerted anti\u2010hypertrophic effects not only in infarcted rat hearts but also in pressure\u2010overloaded mouse hearts. KR<\/jats:styled-content>36676 could be a valuable pharmacological tool in elucidating the complicated physiological role of U<\/jats:styled-content>\u2010II<\/jats:styled-content> and UT<\/jats:styled-content> receptors in cardiac hypertrophy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13082","type":"journal-article","created":{"date-parts":[[2015,1,19]],"date-time":"2015-01-19T07:21:22Z","timestamp":1421652082000},"page":"2618-2633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The orally active urotensin receptor antagonist, KR<\/scp>36676, attenuates cellular and cardiac hypertrophy"],"prefix":"10.1111","volume":"172","author":[{"given":"K S","family":"Oh","sequence":"first","affiliation":[{"name":"Research Center for Drug Discovery Technology Korea Research Institute of Chemical Technology Daejeon Korea"},{"name":"Department of Medicinal and Pharmaceutical Chemistry University of Science and Technology 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Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Technology College of Engineering Sangmyung University Cheonan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C H","family":"Park","sequence":"additional","affiliation":[{"name":"Research Center for Drug Discovery Technology Korea Research Institute of Chemical Technology Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H W","family":"Seo","sequence":"additional","affiliation":[{"name":"Research Center for Drug Discovery Technology Korea Research Institute of Chemical Technology Daejeon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B H","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Center for Drug Discovery Technology Korea Research Institute of Chemical Technology Daejeon Korea"},{"name":"Graduate School of New Drug 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