{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:15:50Z","timestamp":1792498550895,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T00:00:00Z","timestamp":1528070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation program of China","award":["81503497"],"award-info":[{"award-number":["81503497"]}]},{"name":"Fujian Provincial Natural Science fund subject of China","award":["2015J01340"],"award-info":[{"award-number":["2015J01340"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Activating Liver X receptors (LXRs) represents a promising therapeutic option for dyslipidemia. However, activating LXR\u03b1 may cause undesired lipogenic effects. Discovery of highly LXR\u03b2-selective agonists without LXR\u03b1 activation were indispensable for dyslipidemia. In this study, in silico approaches were applied to develop highly potent LXR\u03b2-selective agonists based on a series of newly reported 3-(4-(2-propylphenoxy)butyl)imidazolidine-2,4-dione-based LXR\u03b1\/\u03b2 dual agonists. Initially, Kohonen and stepwise multiple linear regression SW-MLR were performed to construct models for LXR\u03b2 agonists and LXR\u03b1 agonists based on the structural characteristics of LXR\u03b1\/\u03b2 dual agonists, respectively. The obtained LXR\u03b2 agonist model gave a good predictive ability (R2train = 0.837, R2test = 0.843, Q2LOO = 0.715), and the LXR\u03b1 agonist model produced even better predictive ability (R2train = 0.968, R2test = 0.914, Q2LOO = 0.895). Also, the two QSAR models were independent and can well distinguish LXR\u03b2 and LXR\u03b1 activity. Then, compounds in the ZINC database met the lower limit of structural similarity of 0.7, compared to the 3-(4-(2-propylphenoxy)butyl)imidazolidine-2,4-dione scaffold subjected to our QSAR models, which resulted in the discovery of ZINC55084484 with an LXR\u03b2 prediction value of pEC50 equal to 7.343 and LXR\u03b1 prediction value of pEC50 equal to \u22121.901. Consequently, nine newly designed compounds were proposed as highly LXR\u03b2-selective agonists based on ZINC55084484 and molecular docking, of which LXR\u03b2 prediction values almost exceeded 8 and LXR\u03b1 prediction values were below 0.<\/jats:p>","DOI":"10.3390\/molecules23061349","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T12:14:30Z","timestamp":1528114470000},"page":"1349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identfication of Potent LXR\u03b2-Selective Agonists without LXR\u03b1 Activation by In Silico Approaches"],"prefix":"10.3390","volume":"23","author":[{"given":"Meimei","family":"Chen","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"},{"name":"College of Chemistry and Materials Science, Fujian Normal University, Fuzhou 350007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fafu","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science, Fujian Normal University, Fuzhou 350007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Gan","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmei","family":"Lai","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1006\/pmed.1998.0340","article-title":"A low prevalence of coronary heart disease among subjects with increased high-density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency","volume":"27","author":"Moriyama","year":"2016","journal-title":"Prev. 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