Evidence map›Paper›PMID 40236550›Full record

ArticleACS medicinal chemistry letters2025

Fragment-Based Discovery of Drug-like LRH-1 Agonists.

Alisa Lang, Niklas Ildefeld, Felix F Lillich, Astrid Kaiser, Romy Busch, Julian A Marschner, Ewgenij Proschak, Jan Heering, Manfred Schubert-Zsilavecz, Daniel Merk

Abstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2025. 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

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

10 authors.

Alisa LangInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, 60438 Frankfurt, Germany.
Niklas IldefeldInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, 60438 Frankfurt, Germany.
Felix F LillichFraunhofer Institute for Translational Medicine and Pharmacology ITMP, 60596 Frankfurt, Germany.
Astrid KaiserInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, 60438 Frankfurt, Germany.
Romy BuschDepartment of Pharmacy, Ludwig-Maximilians-Universität (LMU) München, 81377 Munich, Germany.
Julian A MarschnerDepartment of Pharmacy, Ludwig-Maximilians-Universität (LMU) München, 81377 Munich, Germany.
Ewgenij ProschakInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, 60438 Frankfurt, Germany.ORCID https://orcid.org/0000-0003-1961-1859
Jan HeeringFraunhofer Institute for Translational Medicine and Pharmacology ITMP, 60596 Frankfurt, Germany.ORCID https://orcid.org/0000-0002-4922-1993
Manfred Schubert-ZsilaveczInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, 60438 Frankfurt, Germany.
Daniel MerkInstitute of Pharmaceutical Chemistry, Goethe University Frankfurt, 60438 Frankfurt, Germany.ORCID https://orcid.org/0000-0002-5359-8128

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The phospholipid sensing transcription factor liver receptor homologue 1 (LRH-1) participates in the transcriptional regulation of metabolic balance and inflammation in liver, pancreas, and other tissues. It is an emerging target for metabolic dysfunction, fatty liver disease, and cancer, but LRH-1 modulators are rare and lack drug-like properties. We discovered new LRH-1 ligands with improved physicochemical features in a fragment-based approach and optimized a venlafaxine-related lead for LRH-1 activation. Despite a strict structure-activity relationship, systematic structural variation resulted in a new LRH-1 agonist scaffold with strong activation efficacy, validated direct and cellular target engagement, and anti-inflammatory and ER-stress-resolving properties in functional cellular settings.

Identifiers

PMID40236550
PMCPMC11995229

What OpenQuestion holds

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Registered trials

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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.