Evidence mapPaperPMID 41000830Full record

ArticlebioRxiv : the preprint server for biology2025

In search of nonlipogenic ABCA1 inducers (NLAI): precision coregulator TR-FRET identifies diverse signatures for LXR ligands.

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

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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, AZ, 85721.ORCID 0000-0002-9803-3323
Martha Ackerman-BerrierDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Fahmida AlamDepartment of Chemistry & Biochemistry, Colleges of Science & Medicine, University of Arizona, Tucson, AZ, 85721.
Sarah TurnerDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Ganga Reddy VelmaDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Christopher PentonDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Soumya Reddy MuskuDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Manan RanaDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Senthil KumarDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Anandhan AnnaduraiDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Maha Ibrahim SulaimanDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Nina MaDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.
Gregory R J ThatcherDepartment of Pharmacology & Toxicology, R Ken Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA.ORCID 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
NIA NIH HHS U01 AG076450NIGMS NIH HHS T32 GM008804
6 · The paper itself

Abstract

APOE4, the major genetic risk factor for Alzheimer's disease (AD), and 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, and inverse agonist signatures within the same chemical series, suggesting the scope for precision CRT to guide nonlipogenic LXR agonist design.

Indexed as

ABCA1coregulatorlipogenesisLXRNuclear receptor

Identifiers

PMID41000830
PMCPMC12458303

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.