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Auraptene (AUR) is a new FXR agonist with excellent safety and extensive pharmacological activities, while the lactone of AUR is vulnerable to esterolysis. In this study, the lactone of AUR was converted to metabolically stable amide moiety, and the obtained analog SU5 revealed comparable activity and better metabolic stability than that of AUR. In NASH model, SU5 showed stronger efficacy than AUR on fatty liver by upregulating gene expressions related to FXR in vivo. Moreover, SU5 improved lipid metabolism by downregulating the gene expressions of lipid synthesis, while upregulating the gene expressions of fatty acid \u03b2\u2010oxidation and triglyceride metabolism. Besides, the inflammation\u2010related genes were significantly decreased in SU5\u2010treated group. These positive results highlighted the pharmacological potential of SU5 for the treatment of NASH.<\/jats:p>","DOI":"10.1111\/cbdd.14021","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T04:43:15Z","timestamp":1642480995000},"page":"504-511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["SU5, a new Auraptene analog with improved metabolic stability, ameliorates nonalcoholic fatty liver disease in methionine\u2010 and choline\u2010deficient diet\u2010fed <i>db\/db<\/i> mice"],"prefix":"10.1111","volume":"99","author":[{"given":"Fen","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Infectious Disease The First Affiliated Hospital of Soochow University  Suzhou China"},{"name":"Department of General Practice Yancheng First People\u2019s Hospital  Yancheng City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DeZhi","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of General Practice Yancheng First People\u2019s Hospital  Yancheng City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"XuDong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of General Practice Yancheng First People\u2019s Hospital  Yancheng City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RuoBing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Practice Yancheng First People\u2019s Hospital  Yancheng City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ChaoNan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Practice Yancheng First People\u2019s Hospital  Yancheng City China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JianHe","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2012.05.012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10113206"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.11.021"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026614666141112094058"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28719"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2019_227"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2017.09.016"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8FO00107C"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026614666141112100208"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00051-4"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-016-0812-y"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0264-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.06.009"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.18-3-245"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23719"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509840"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023745"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.11.043"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01701"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13135"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1665-2681(19)31530-3"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728214.2020.1796968"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-017-1415-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.044"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9FO00318E"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109609"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00342"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29724"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.11.015"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.7.3818"}],"container-title":["Chemical Biology &amp; 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