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In addition to enhanced reverse cholesterol transport, however, LXR activation induces hepatic lipogenesis. Since the subtype LXR\u03b1 is dominant in the liver, one strategy to overcome this is the development of LXR\u03b2\u2010selective agonists. We optimized the reported compound\n                    <jats:bold>2<\/jats:bold>\n                    with efficacy\u2010based preference for LXR\u03b2 by scaffold hopping to enhance potency and selectivity. Among the four different scaffolds, which were obtained from computer\u2010assisted design and subsequent synthesis, compound\n                    <jats:bold>7<\/jats:bold>\n                    emerged as the most promising scaffold. The spiro[indan\u20101,4\u2032\u2010piperidine] scaffold of\n                    <jats:bold>7<\/jats:bold>\n                    demonstrated superior pharmacokinetic and pharmacodynamic properties, warranting its further investigation towards a pharmacological tool compound.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70509","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:10:42Z","timestamp":1791439842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Scaffold Hopping Provides Liver X Receptor Agonist With Preference for the \u03b2 Subtype"],"prefix":"10.1002","volume":"21","author":[{"given":"Annette","family":"K\u00e4rcher","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona L.","family":"Motel","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8800-7584","authenticated-orcid":false,"given":"Felix F.","family":"Lillich","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1961-1859","authenticated-orcid":false,"given":"Ewgenij","family":"Proschak","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5187-6342","authenticated-orcid":false,"given":"Pascal","family":"Heitel","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27883.LXRs"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.9.1033"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000879200"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.2.121"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm500442z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.a.20015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108225200"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm070453f"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.04.012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100034x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00176"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b02029"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.6b00234"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.05.048"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600305"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2018.03.013"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009335768"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CMET.2016.07.016"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100029\u20101217818"},{"key":"e_1_2_9_23_1","unstructured":"M. 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