ArticleCell chemical biology2022
A phospholipid mimetic targeting LRH-1 ameliorates colitis.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Microbiome-host communication via vaccenic acid modulates LRH-1/NR5A2 activity and ameliorates metabolic liver disease.EMBO molecular medicine · 2026Article
- From hepatic to hematopoietic: LRH-1's expanding cellular repertoire to the immune system.The FEBS journal · 2026Review
- Structure-guided compound prioritization strategy for virtual screening identifies putative binders for the nuclear receptor LRH-1.bioRxiv : the preprint server for biology · 2026Article
- Impact of Bile Acid Amidation on In Silico Farnesoid X Receptor Dynamics.The journal of physical chemistry. B · 2025Article
- Fragment-Based Discovery of Drug-like LRH-1 Agonists.ACS medicinal chemistry letters · 2025Article
- Fatty Acid Mimetic Fragments as Liver Receptor Homologue-1 Modulators.ACS pharmacology & translational science · 2025Article
- A novel heuristic of rigid docking scores positively correlates with full-length nuclear receptor LRH-1 regulation.Computational and structural biotechnology journal · 2024Article
- The nuclear receptor LRH-1 discriminates between ligands using distinct allosteric signaling circuits.Protein science : a publication of the Protein Society · 2023Article
- New High-Throughput Screen Discovers Novel Ligands of Full-Length Nuclear Receptor LRH-1.ACS chemical biology · 2023Article
- Asparagine protects pericentral hepatocytes during acute liver injury.The Journal of clinical investigation · 2023Article
- Differential Modulation of Nuclear Receptor LRH-1 through Targeting Buried and Surface Regions of the Binding Pocket.Journal of medicinal chemistry · 2022Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Phospholipids are ligands for nuclear hormone receptors (NRs) that regulate transcriptional programs relevant to normal physiology and disease. Here, we demonstrate that mimicking phospholipid-NR interactions is a robust strategy to improve agonists of liver receptor homolog-1 (LRH-1), a therapeutic target for colitis. Conventional LRH-1 modulators only partially occupy the binding pocket, leaving vacant a region important for phospholipid binding and allostery. Therefore, we constructed a set of molecules with elements of natural phospholipids appended to a synthetic LRH-1 agonist. We show that the phospholipid-mimicking groups interact with the targeted residues in crystal structures and improve binding affinity, LRH-1 transcriptional activity, and conformational changes at a key allosteric site. The best phospholipid mimetic markedly improves colonic histopathology and disease-related weight loss in a murine T cell transfer model of colitis. This evidence of in vivo efficacy for an LRH-1 modulator in colitis represents a leap forward in agonist development.
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Registered trials
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.