ArticleNature communications2019
Molecular tuning of farnesoid X receptor partial agonism.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 98 citations in OpenAlex.
- RT206 Couples Partial PPARα/γ Agonism with Ligand-Dependent Allosteric Potentiation of FXR Signaling in Liver Cells.Biomolecules · 2026Article
- Structural and evolutionary insights into DAF-12 interactions with transcriptional coactivators in parasitic nematodes.PLoS pathogens · 2026Article
- Discovery of sulfonyl benzoic acid derivatives with joint TGR5-agonist and FXR-antagonist activity for myocardial ischemia/reperfusion injury protection.Acta pharmaceutica Sinica. B · 2026Article
- CDCA-Derived NE3TA Conjugate for Liver-SelectiveACS omega · 2026Article
- Evolutionary remodeling of the FXR binding pocket drove functional divergence and ligand discrimination.Molecular biology and evolution · 2026Article
- A Review on Farnesoid X Receptor (FXR) Modulators Focusing on Benzimidazole Scaffold.Molecules (Basel, Switzerland) · 2026Review
- Structure-Based Discovery of Obeticholic Acid Derivatives as Novel Farnesoid X Receptor Partial Agonists with Improved Selectivity and Reduced Off-Target Effects.ChemMedChem · 2026Article
- Impact of Bile Acid Amidation on In Silico Farnesoid X Receptor Dynamics.The journal of physical chemistry. B · 2025Article
- Development of cyclopeptide inhibitors specifically disrupting FXR-coactivator interaction in the intestine as a novel therapeutic strategy for MASH.Life metabolism · 2025Article
- Structural basis for the asymmetric binding of coactivator SRC1 to FXR-RXRα and allosteric communication within the complex.Communications biology · 2025Article
- Simulations Reveal Unique Roles for the FXR Hinge in the FXR-RXR Nuclear Receptor Heterodimer.ACS bio & med chem Au · 2025Article
- Impact of Replicas and Simulation Length on In Silico Behaviors of a Protein Domain.Chemphyschem : a European journal of chemical physics and physical chemistry · 2025Article
- An overview of basic pathophysiological interactions between gut bacteria and their host.Frontiers in nutrition · 2025Review
- The Molecular Mechanism of Farnesoid X Receptor Alleviating Glucose Intolerance in Turbot (Cells · 2024Article
- Farnesoid X receptor: From Structure to Function and Its Pharmacology in Liver Fibrosis.Aging and disease · 2024Review
- On the Cholesterol Raising Effect of Coffee Diterpenes Cafestol and 16-International journal of molecular sciences · 2024Article
- 3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists.Molecules (Basel, Switzerland) · 2024Article
- Drug targets regulate systemic metabolism and provide new horizons to treat nonalcoholic steatohepatitis.Metabolism open · 2024Review
- Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy.International journal of molecular sciences · 2023Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bile acid-sensing transcription factor farnesoid X receptor (FXR) regulates multiple metabolic processes. Modulation of FXR is desired to overcome several metabolic pathologies but pharmacological administration of full FXR agonists has been plagued by mechanism-based side effects. We have developed a modulator that partially activates FXR in vitro and in mice. Here we report the elucidation of the molecular mechanism that drives partial FXR activation by crystallography- and NMR-based structural biology. Natural and synthetic FXR agonists stabilize formation of an extended helix α11 and the α11-α12 loop upon binding. This strengthens a network of hydrogen bonds, repositions helix α12 and enables co-activator recruitment. Partial agonism in contrast is conferred by a kink in helix α11 that destabilizes the α11-α12 loop, a critical determinant for helix α12 orientation. Thereby, the synthetic partial agonist induces conformational states, capable of recruiting both co-repressors and co-activators leading to an equilibrium of co-activator and co-repressor binding.
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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.