Evidence map›Paper›PMID 42844903›Full record

ArticleChemMedChem2026

Scaffold Hopping Provides Liver X Receptor Agonist With Preference for the β Subtype.

Annette Kärcher, Fiona L Motel, Felix F Lillich, Astrid Kaiser, Ewgenij Proschak, Pascal Heitel

Abstract read
In one paragraph

Article in ChemMedChem, 2026. 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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Annette KärcherInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.
Fiona L MotelInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.
Felix F LillichInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.ORCID https://orcid.org/0009-0009-8800-7584
Astrid KaiserInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.
Ewgenij ProschakInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.ORCID https://orcid.org/0000-0003-1961-1859
Pascal HeitelInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany.ORCID https://orcid.org/0000-0001-5187-6342

Funding

Detlef Hübner StiftungHans und Ria Messer Stiftung Z_HMS_11/022 Goethe Universität FFM_Dr. HeitelStiftung Polytechnische Gesellschaft Frankfurt
6 · The paper itself

Abstract

The liver X receptor is a promising target for diseases with dysregulated cholesterol levels. In addition to enhanced reverse cholesterol transport, however, LXR activation induces hepatic lipogenesis. Since the subtype LXRα is dominant in the liver, one strategy to overcome this is the development of LXRβ-selective agonists. We optimized the reported compound 2 with efficacy-based preference for LXRβ by scaffold hopping to enhance potency and selectivity. Among the four different scaffolds, which were obtained from computer-assisted design and subsequent synthesis, compound 7 emerged as the most promising scaffold. The spiro[indan-1,4'-piperidine] scaffold of 7 demonstrated superior pharmacokinetic and pharmacodynamic properties, warranting its further investigation towards a pharmacological tool compound.

Indexed as

IndansLiver X ReceptorsOrphan Nuclear ReceptorsPiperidinesSpiro CompoundsAnimalsHumansMolecular StructureStructure-Activity RelationshipIndansLiver X ReceptorsNR1H3 protein, humanOrphan Nuclear ReceptorsPiperidinesSpiro Compoundsdrug designdrug discoveryfunctional selectivitymedicinal chemistryspiro compounds

Identifiers

PMID42844903
PMCPMC13646660

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.