Evidence mapPaperPMID 42325211Full record

ArticleeLife2026

Exploration of precision coregulator TR-FRET identifies diverse signatures for LXR ligands relevant to discovery of nonlipogenic ABCA1 inducers.

Megan S Laham, Martha S Ackerman-Berrier, Fahmida Alam, Sarah Turner, Ganga Reddy Velma, Christopher Penton, Soumya Reddy Musku, Manan Rana, Senthilkumar Thulasingam, Anandhan Annadurai and 3 more

Abstract read
In one paragraph

Article in eLife, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Megan S LahamDepartment of Chemistry & Biochemistry, Colleges of Science & Medicine, University of Arizona, Tucson, United States.ORCID https://orcid.org/0000-0002-9803-3323
Martha S Ackerman-BerrierDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.
Fahmida AlamDepartment of Chemistry & Biochemistry, Colleges of Science & Medicine, University of Arizona, Tucson, United States.ORCID https://orcid.org/0009-0007-3369-6584
Sarah TurnerDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.
Ganga Reddy VelmaDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.ORCID https://orcid.org/0000-0001-5054-2519
Christopher PentonDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.
Soumya Reddy MuskuDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.
Manan RanaDepartment of Chemistry & Biochemistry, Colleges of Science & Medicine, University of Arizona, Tucson, United States.ORCID https://orcid.org/0009-0002-3636-8934
Senthilkumar ThulasingamDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.
Anandhan AnnaduraiDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.
Maha Ibrahim SulaimanDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.
Nina MaDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, United States.
Gregory R J ThatcherDepartment of Chemistry & Biochemistry, Colleges of Science & Medicine, University of Arizona, Tucson, United States.ORCID https://orcid.org/0000-0002-7757-1739

Funding

Nonlipogenic ABCA1 inducers for ADRDU01AG076450 · UNIVERSITY OF ARIZONA · 2025 to 2025
$729k
CHEMICAL-BIOLOGY INTERFACE TRAINING GRANTT32GM008804 · UNIVERSITY OF ARIZONA · 2003 to 2005
$326k
NIH HHS T32GM008804NIH HHS U01AG076450
6 · The paper itself

Abstract

APOE4, the major genetic risk factor for Alzheimer's disease (AD), and ATP-binding cassette-A1 (ABCA1), required for lipidation of APOE are gene products of the liver X receptor (LXR) receptor. 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 LXRβ 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, inverse agonist, and other signatures within the same chemical series, suggesting the scope for precision CRT to guide nonlipogenic LXR agonist design.

Indexed as

ATP Binding Cassette Transporter 1Liver X ReceptorsFluorescence Resonance Energy TransferHumansLigandsABCA1 protein, humanATP Binding Cassette Transporter 1LigandsLiver X ReceptorsATP-binding cassette-A1biochemistrychemical biologycoregulator selectivitylipogenesisliver X receptorLXRnone

Identifiers

PMID42325211
PMCPMC13286573

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.