{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T04:37:37Z","timestamp":1769834257309,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T00:00:00Z","timestamp":1520467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We attempted to clarify the therapeutic capability of antagonists of the farnesoid X receptor (<jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content>), a nuclear receptor that regulates lipid and bile acid metabolism. Herein, we report the antidyslipidemic effects of a novel synthesized <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content> antagonist, compound\u2010T1, utilizing a dyslipidemic hamster model. Compound\u2010T1 selectively inhibited chenodeoxycholic acid\u2010induced <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content> activation (<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub>, 2.1\u00a0nmol\u00b7L<jats:sup>\u22121<\/jats:sup>). A hamster model of diet\u2010induced hyperlipidemia was prepared to investigate the antidyslipidemic effects of compound\u2010T1 through comparative studies of the nonstatin lipid\u2010modulating agents ezetimibe, cholestyramine, and torcetrapib. In the hamster model, compound\u2010T1 (6\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, p.o.) increased the level of plasma high\u2010density lipoprotein (<jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>)\u2010cholesterol (+22.2%) and decreased the levels of plasma non\u2010<jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010cholesterol (\u221243.6%) and triglycerides (\u221231.1%). Compound\u2010T1 also increased hepatic cholesterol 7\u03b1\u2010hydroxylase expression and fecal bile acid excretion, and decreased hepatic cholesterol content. Moreover, the hamster model could reflect clinical results of other nonstatin agents. Torcetrapib especially increased large <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> particles compared with compound\u2010T1. Additionally, in the human hepatoma Huh\u20107 cells, compound\u2010T1 enhanced apolipoprotein A\u2010I secretion at a concentration close to its <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> value for <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content>. Our results indicated the usefulness of the hamster model in evaluating <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content> antagonists and nonstatin agents. Notably, compound\u2010T1 exhibited beneficial effects on both blood non\u2010<jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010cholesterol and <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010cholesterol, which are thought to involve enhancement of cholesterol catabolism and apolipoprotein A\u2010I production. These findings aid the understanding of the antidyslipidemic potential of <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content> antagonists with a unique lipid and bile acid modulation.<\/jats:p>","DOI":"10.1002\/prp2.390","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T10:50:46Z","timestamp":1520506246000},"source":"Crossref","is-referenced-by-count":5,"title":["Antidyslipidemic potential of a novel farnesoid X receptor antagonist in a hamster model of dyslipidemia: Comparative studies of other nonstatin agents"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5059-1895","authenticated-orcid":false,"given":"Emiko","family":"Shinozawa","sequence":"first","affiliation":[{"name":"Research Takeda Pharmaceutical Company Limited Fujisawa Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichiro","family":"Amano","sequence":"additional","affiliation":[{"name":"Research Takeda Pharmaceutical Company Limited Fujisawa Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Yamakawa","sequence":"additional","affiliation":[{"name":"Research Takeda Pharmaceutical Company Limited Fujisawa Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Haba","sequence":"additional","affiliation":[{"name":"Research Takeda Pharmaceutical Company Limited Fujisawa Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuyuki","family":"Shimada","sequence":"additional","affiliation":[{"name":"Research Takeda Pharmaceutical Company Limited Fujisawa Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuichi","family":"Tozawa","sequence":"additional","affiliation":[{"name":"Research Takeda Pharmaceutical Company Limited Fujisawa Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.303.6797.276"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61778-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67394-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-668X(02)00419-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41379-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-7-201304020-00004"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.69.2.313"},{"key":"e_1_2_9_9_1","first-page":"365","article-title":"The lipid research clinics coronary primary prevention trial results: II. 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