ArticleLiver international : official journal of the International Association for the Study of the Liver2020
A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Obeticholic Acid and Edaravone Protect Against Cisplatin-Induced Hepatotoxicity Through Modulation of Keap1/Nrf2/ARE, TNF-α/NF-κB, and AKT/GSK-3β Pathways.Journal of biochemical and molecular toxicology · 2026Article
- Review
- Unveiling a novel macrophage-driven mechanism for obeticholic acid-induced liver injury in cholestatic: targeting NLRP12Cell biology and toxicology · 2026Article
- Article
- Unravelling the therapeutic landscape of bile acid-based therapies in gastrointestinal disorders.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2024Review
- Non-steroidal FXR agonist cilofexor improves cholestatic liver injury in theJHEP reports : innovation in hepatology · 2023Article
- Persistent Lipid Accumulation Leads to Persistent Exacerbation of Endoplasmic Reticulum Stress and Inflammation in Progressive NASH via the IRE1α/TRAF2 Complex.Molecules (Basel, Switzerland) · 2023Article
- Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?Frontiers in immunology · 2023Review
- The ameliorating effect of withaferin A on high-fat diet-induced non-alcoholic fatty liver disease by acting as an LXR/FXR dual receptor activator.Frontiers in pharmacology · 2023Article
- Assessment of drug-drug interaction potential with EDP-305, a farnesoid X receptor agonist, in healthy subjects.Clinical and translational science · 2022Article
- Targeting fibrosis, mechanisms and cilinical trials.Signal transduction and targeted therapy · 2022Review
- Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: Current Knowledge of Pathogenesis and Therapeutics.Biomedicines · 2022Review
- Liver Steatosis: A Marker of Metabolic Risk in Children.International journal of molecular sciences · 2022Review
- The gut-liver axis in cholangiopathies: focus on bile acid based pharmacological treatment.Current opinion in gastroenterology · 2022Review
- Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates.Biomedicines · 2022Review
- Changes in beta-catenin expression and activation during progression of primary sclerosing cholangitis predict disease recurrence.Scientific reports · 2022Article
- Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus.Nature reviews. Endocrinology · 2021Review
- Liver-targeting drugs and their effect on blood glucose and hepatic lipids.Diabetologia · 2021Review
- Nonalcoholic Fatty Liver Disease (NAFLD). Mitochondria as Players and Targets of Therapies?International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundEDP-305 is a novel and potent farnesoid X receptor (FXR) agonist, with no/minimal cross-reactivity to TGR5 or other nuclear receptors. Herein we report therapeutic efficacy of EDP-305, in direct comparison with the first-in-class FXR agonist obeticholic acid (OCA), in mouse models of liver disease.
methodsEDP-305 (10 and 30 mg/kg/day) or OCA (30mg/kg/day) was tested in mouse models of pre-established biliary fibrosis (BALBc.Mdr2-/-, n = 9-12/group) and steatohepatitis induced by methionine/choline-deficient diet (MCD, n = 7-12/group). Effects on biliary epithelium were evaluated in vivo and in primary EpCAM + hepatic progenitor cell (HPC) cultures.
resultsIn a BALBc.Mdr2-/- model, EDP-305 reduced serum transaminases by up to 53% and decreased portal pressure, compared to untreated controls. Periportal bridging fibrosis was suppressed by EDP-305 at both doses, with up to a 39% decrease in collagen deposition in high-dose EDP-305. In MCD-fed mice, EDP-305 treatment reduced serum ALT by 62% compared to controls, and profoundly inhibited perisinusoidal 'chicken wire' fibrosis, with over 80% reduction in collagen deposition. In both models, treatment with 30mg/kg OCA reduced serum transaminases up to 30%, but did not improve fibrosis. The limited impact on fibrosis was mediated by cholestasis-independent worsening of ductular reaction by OCA in both disease models; OCA but not EDP-305 at therapeutic doses promoted ductular proliferation in healthy mice and favoured differentiation of primary HPC towards cholangiocyte lineage in vitro.
conclusionsEDP-305 potently improved pre-established liver injury and hepatic fibrosis in murine biliary and metabolic models of liver disease, supporting the clinical evaluation of EDP-305 in fibrotic liver diseases including cholangiopathies and non-alcoholic steatohepatitis.
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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.