Related Experiment Video

Updated: May 27, 2025

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
07:32

Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library

Published on: September 30, 2019

7.6K

Farnesoid X receptor and fibroblast growth factor 15/19 as pharmacological targets

Syeda Maliha1, Grace L Guo1,2,3,4,5

  • 1Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA.

Liver Research
|February 17, 2025
PubMed

Insights

Farnesoid X receptor (FXR) agonists and FGF19 analogs show promise for treating non-alcoholic steatohepatitis (NASH). Research is exploring FXR antagonism as well, with several drug candidates in preclinical and clinical development for this liver disease.

Area of Science:

  • Hepatology
  • Endocrinology
  • Pharmacology

Background:

  • The farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid and cholesterol homeostasis, crucial in liver and intestinal functions.
  • Dysregulation of FXR signaling contributes to non-alcoholic steatohepatitis (NASH), a progressive liver disease with no current FDA-approved treatments.
  • Fibroblast growth factor 15 (FGF15) in mice and FGF19 in humans, an FXR target gene, plays a role in these metabolic pathways.

Purpose of the Study:

  • To review current therapeutic strategies targeting bile acid signaling for non-alcoholic steatohepatitis (NASH).
  • To focus on preclinical and clinical research of FXR agonists and FGF19 analogs in NASH treatment.
  • To evaluate the potential of FXR antagonism as a therapeutic approach for NASH.

Main Methods:

  • Literature review of preclinical studies in mice and clinical trials in humans.
  • Analysis of the role of FXR and its target gene FGF19 in NASH pathogenesis.
  • Evaluation of FXR agonists, FGF19 analogs, and FXR antagonists in NASH treatment.

Main Results:

  • Several synthetic FXR agonists (e.g., OCA, cilofexor) and FGF19 analogs (e.g., NGM282) are in clinical trials for NASH.
  • FXR antagonism using agents like UDCA and Gly-MCA is under preclinical investigation for NASH.
  • Bile acid regulation is a key factor in NASH pathophysiology, making FXR a significant therapeutic target.

Conclusions:

  • FXR modulation, through agonists or antagonists, represents a promising therapeutic avenue for NASH.
  • Targeting bile acid signaling pathways offers potential for treating NASH, a condition with significant unmet medical needs.
  • Ongoing clinical trials will determine the efficacy and safety of FXR-targeted therapies for NASH patients.
Keywords:
Bile acidsFarnesoid X receptor (FXR)Fibroblast growth factor 15 (FGF15)Fibroblast growth factor 19 (FGF19)Non-alcoholic steatohepatitis (NASH)

More Related Videos

An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation08:48

An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation

Published on: June 30, 2015

8.2K
An Automated Radiosynthesis of [68Ga]Ga-FAPI-46 for Routine Clinical Use10:33

An Automated Radiosynthesis of [68Ga]Ga-FAPI-46 for Routine Clinical Use

Published on: May 24, 2024

664

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.3K
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
1.8K
Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.0K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K