FXR: structures, biology, and drug development for NASH and fibrosis diseases

A structurally optimized FXR agonist, MET409, reduced liver fat content over 12 weeks in patients with non-alcoholic steatohepatitis

(2021) Stephen A. Harrison et al.   JOURNAL OF HEPATOLOGY

Intestine-specific FXR agonists as potential therapeutic agents for colorectal cancer

(2021) Yiming Yin et al.   BIOCHEMICAL PHARMACOLOGY

Safety, Pharmacokinetics, Pharmacodynamics, and Formulation of Liver‐Distributed Farnesoid X‐Receptor Agonist TERN‐101 in Healthy Volunteers

(2021) Yujin Wang et al.   Clinical Pharmacology in Drug Development

Cilofexor, a Nonsteroidal FXR Agonist, in Non‐Cirrhotic Patients with Nonalcoholic Steatohepatitis: A Phase 2 Randomized Controlled Trial

(2020) Keyur Patel et al.   HEPATOLOGY

Emerging drugs for the treatment of non-alcoholic steatohepatitis: a focused review of farnesoid X receptor agonists

(2020) Raj A. Shah et al.   EXPERT OPINION ON EMERGING DRUGS

Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH)

(2020) Stefano Fiorucci et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Structural basis of tropifexor as a potent and selective agonist of farnesoid X receptor

(2020) Longying Jiang et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH

(2020) Rohit Loomba et al.   HEPATOLOGY

Molecular tuning of farnesoid X receptor partial agonism

(2019) Daniel Merk et al.   Nature Communications

REGENERATE: Design of a pivotal, randomised, phase 3 study evaluating the safety and efficacy of obeticholic acid in patients with fibrosis due to nonalcoholic steatohepatitis

(2019) Vlad Ratziu et al.   Contemporary Clinical Trials

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

(2019) Zobair M Younossi et al.   LANCET

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Non–Bile Acid FXR Agonist Tropifexor (LJN452) in Healthy Volunteers

(2019) Michael K. Badman et al.   Clinical Pharmacology in Drug Development

Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

(2019) Joost Boeckmans et al.   Cells

Farnesoid X receptor modulators 2014-present: a patent review

(2018) Valentina Sepe et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Update on FXR Biology: Promising Therapeutic Target?

(2018) Chang Han   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Structural insights into the heterodimeric complex of the nuclear receptors FXR and RXR

(2018) Weili Zheng et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Future trends in the treatment of non-alcoholic steatohepatitis

(2018) Stefano Fiorucci et al.   PHARMACOLOGICAL RESEARCH

Progress and challenges of selective Farnesoid X Receptor modulation

(2018) Vittoria Massafra et al.   PHARMACOLOGY & THERAPEUTICS

Farnesoid X receptor agonist INT-767 attenuates liver steatosis and inflammation in rat model of nonalcoholic steatohepatitis

(2018) Ying-Bin Hu et al.   Drug Design Development and Therapy

FXR modulators for enterohepatic and metabolic diseases

(2018) Hong Wang et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Ligand binding and heterodimerization with retinoid X receptor α (RXRα) induce farnesoid X receptor (FXR) conformational changes affecting coactivator binding

(2018) Na Wang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Current and future pharmacological therapies for NAFLD/NASH

(2017) Yoshio Sumida et al.   JOURNAL OF GASTROENTEROLOGY

Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH)

(2017) David C. Tully et al.   JOURNAL OF MEDICINAL CHEMISTRY

Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models

(2017) Mukul R. Jain et al.   LIVER INTERNATIONAL

Targeting nuclear receptors for the treatment of fatty liver disease

(2017) Naoki Tanaka et al.   PHARMACOLOGY & THERAPEUTICS

Synthesis and Biological Evaluation of a Series of Bile Acid Derivatives as FXR Agonists for Treatment of NASH

(2017) Hualing Xiao et al.   ACS Medicinal Chemistry Letters

Nuclear receptors and nonalcoholic fatty liver disease 1 1This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

(2016) Matthew C. Cave et al.   Biochimica et Biophysica Acta-Gene Regulatory Mechanisms

Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: Understanding and improving key determinants of pharmacological properties

(2016) Olaf Kinzel et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Farnesoid X Receptor Agonists and Other Bile Acid Signaling Strategies for Treatment of Liver Disease

(2016) Emina Halilbasic et al.   DIGESTIVE DISEASES

Novel Pharmacotherapy Options for NASH

(2016) Vlad Ratziu   DIGESTIVE DISEASES AND SCIENCES

Recent Progress on Bile Acid Receptor Modulators for Treatment of Metabolic Diseases

(2016) Yanping Xu   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 3α,7α,11β-Trihydroxy-6α-ethyl-5β-cholan-24-oic Acid (TC-100), a Novel Bile Acid as Potent and Highly Selective FXR Agonist for Enterohepatic Disorders

(2016) Roberto Pellicciari et al.   JOURNAL OF MEDICINAL CHEMISTRY

Fatty liver diseases, bile acids, and FXR

(2016) Yan Zhu et al.   Acta Pharmaceutica Sinica B

Insights on FXR selective modulation. Speculation on bile acid chemical space in the discovery of potent and selective agonists

(2016) Valentina Sepe et al.   Scientific Reports

FXR Agonists as Therapeutic Agents for Non-alcoholic Fatty Liver Disease

(2015) Rotonya M. Carr et al.   Current Atherosclerosis Reports

Structural Basis for Small Molecule NDB (N-Benzyl-N-(3-(tert-butyl)-4-hydroxyphenyl)-2,6-dichloro-4-(dimethylamino) Benzamide) as a Selective Antagonist of Farnesoid X Receptor α (FXRα) in Stabilizing the Homodimerization of the Receptor

(2015) Xing Xu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of 6-(4-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic Acid: A Novel FXR Agonist for the Treatment of Dyslipidemia

(2015) Michael J. Genin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial

(2015) Brent A Neuschwander-Tetri et al.   LANCET

Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance

(2015) Sungsoon Fang et al.   NATURE MEDICINE

Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction

(2015) Changtao Jiang et al.   Nature Communications

Gut Microbiota Regulates Bile Acid Metabolism by Reducing the Levels of Tauro-beta-muricholic Acid, a Naturally Occurring FXR Antagonist

(2013) Sama I. Sayin et al.   Cell Metabolism

The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism

(2013) Lihua Jin et al.   Nature Communications

Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR

(2012) Anna C. Calkin et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Extending SAR of bile acids as FXR ligands: Discovery of 23-N-(carbocinnamyloxy)-3α,7α-dihydroxy-6α-ethyl-24-nor-5β-cholan-23-amine

(2011) Antimo Gioiello et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Selective Activation of Nuclear Bile Acid Receptor FXR in the Intestine Protects Mice Against Cholestasis

(2011) Salvatore Modica et al.   GASTROENTEROLOGY

Structural and functional insights into nuclear receptor signaling

(2010) Lihua Jin et al.   ADVANCED DRUG DELIVERY REVIEWS

Synthesis and pharmacological validation of a novel series of non-steroidal FXR agonists

(2010) Ulrich Abel et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Conformationally constrained farnesoid X receptor (FXR) agonists: Heteroaryl replacements of the naphthalene

(2010) Jonathan Y. Bass et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

2 FARNESOID-X RECEPTOR AGONISTS: A NEW CLASS OF DRUGS FOR THE TREATMENT OF PBC? AN INTERNATIONAL STUDY EVALUATING THE ADDITION OF INT-747 TO URSODEOXYCHOLIC ACID

(2010) A. Mason et al.   JOURNAL OF HEPATOLOGY

Improvement of Physiochemical Properties of the Tetrahydroazepinoindole Series of Farnesoid X Receptor (FXR) Agonists: Beneficial Modulation of Lipids in Primates

(2010) Joseph T. Lundquist et al.   JOURNAL OF MEDICINAL CHEMISTRY

Functional Characterization of the Semisynthetic Bile Acid Derivative INT-767, a Dual Farnesoid X Receptor and TGR5 Agonist

(2010) G. Rizzo et al.   MOLECULAR PHARMACOLOGY

Pyrrole[2,3-d]azepino compounds as agonists of the farnesoid X receptor (FXR)

(2009) John F. Mehlmann et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis

(2009) Songwen Zhang et al.   JOURNAL OF HEPATOLOGY

Discovery of XL335 (WAY-362450), a Highly Potent, Selective, and Orally Active Agonist of the Farnesoid X Receptor (FXR)

(2009) Brenton Flatt et al.   JOURNAL OF MEDICINAL CHEMISTRY

Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation

(2009) Philippe Lefebvre et al.   PHYSIOLOGICAL REVIEWS

Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064

(2008) Adwoa Akwabi-Ameyaw et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Identification of a potent synthetic FXR agonist with an unexpected mode of binding and activation

(2008) S. M. Soisson et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA