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LXR agonists have been validated in animal models as therapeutics for AD, atherosclerosis, and many other diseases. Clinical progress has been thwarted by unwanted hepatic lipogenesis. Structurally diverse LXR ligands were profiled in coregulator TR-FRET (CRT) assays analyzing ligand-induced coactivator recruitment, coactivator selectivity, corepressor dissociation, and LXR isoform selectivity. A multiplex CRT assay was developed to measure synchronous ligand-induced displacement of corepressor by coactivator. Potency for coactivator recruitment to LXR\u03b2 correlated with induction of ABCA1 in human astrocytoma cells. Correlation with lipogenic activation of sterol response element (SRE) in hepatocarcinoma cells, was more complex. CRT response was diverse revealing ligands with theoretical full agonist, partial agonist, antagonist, and inverse agonist, and other signatures within the same chemical series, suggesting the scope for precision CRT to guide nonlipogenic LXR agonist design.<\/jats:p>","DOI":"10.1101\/2025.09.12.675753","type":"posted-content","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T19:10:15Z","timestamp":1758136215000},"source":"Crossref","is-referenced-by-count":1,"title":["In search of nonlipogenic ABCA1 inducers (NLAI): precision coregulator TR-FRET identifies diverse signatures for LXR ligands"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9803-3323","authenticated-orcid":false,"given":"Megan S.","family":"Laham","sequence":"first","affiliation":[{"name":"Department of Chemistry & Biochemistry, Colleges of Science & Medicine, University of Arizona, Tucson, AZ, 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