Abstract
The farnesoid X receptor (FXR) is a nuclear receptor expressed in tissues exposed to high concentrations of bile acids such as the liver, kidney and intestine and functions as a bile acid sensor. FXR regulates the expression of various transport proteins and biosynthetic enzymes crucial to the physiological maintenance of lipids, cholesterol and bile acid homeostasis. The concept of reverse endocrinology, whereby the receptor is identified first, followed by the identification of ligands and the sequential elucidation of the physiological role of the receptor has been widely used for a number of orphan nuclear receptors. The design of synthetic high affinity ligands acting via these receptors not only helps to decipher the function of the receptor, but also should lead to the development of novel and highly specific drugs. The bile acid receptor FXR is a perfect example where this strategy helped with understanding the role of this receptor in cholesterol and bile acid homeostasis. Regulation of FXR through small-molecule drugs represents a promising therapy for diseases resulting from lipid, cholesterol and bile acid abnormalities.
Keywords: farnesoid x receptor, bile acid receptor, nuclear receptor, bile acids, fxr ligands, small molecule drugs, hyperlipidemia, cholestasis
Mini-Reviews in Medicinal Chemistry
Title: FXR, A Therapeutic Target for Bile Acid and Lipid Disorders
Volume: 5 Issue: 8
Author(s): Stefan Westin, Richard A. Heyman and Richard Martin
Affiliation:
Keywords: farnesoid x receptor, bile acid receptor, nuclear receptor, bile acids, fxr ligands, small molecule drugs, hyperlipidemia, cholestasis
Abstract: The farnesoid X receptor (FXR) is a nuclear receptor expressed in tissues exposed to high concentrations of bile acids such as the liver, kidney and intestine and functions as a bile acid sensor. FXR regulates the expression of various transport proteins and biosynthetic enzymes crucial to the physiological maintenance of lipids, cholesterol and bile acid homeostasis. The concept of reverse endocrinology, whereby the receptor is identified first, followed by the identification of ligands and the sequential elucidation of the physiological role of the receptor has been widely used for a number of orphan nuclear receptors. The design of synthetic high affinity ligands acting via these receptors not only helps to decipher the function of the receptor, but also should lead to the development of novel and highly specific drugs. The bile acid receptor FXR is a perfect example where this strategy helped with understanding the role of this receptor in cholesterol and bile acid homeostasis. Regulation of FXR through small-molecule drugs represents a promising therapy for diseases resulting from lipid, cholesterol and bile acid abnormalities.
Export Options
About this article
Cite this article as:
Westin Stefan, Heyman A. Richard and Martin Richard, FXR, A Therapeutic Target for Bile Acid and Lipid Disorders, Mini-Reviews in Medicinal Chemistry 2005; 5 (8) . https://dx.doi.org/10.2174/1389557054553802
DOI https://dx.doi.org/10.2174/1389557054553802 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Therapeutics Targeting Nogo-A Hold Promise for Stroke Restoration
CNS & Neurological Disorders - Drug Targets ESVS Guidelines: Section A - Prevention in Patients with Carotid Stenosis
Current Vascular Pharmacology Peak Treadmill Exercise Echocardiography
Reviews on Recent Clinical Trials BACE1 Structure and Function in Health and Alzheimers Disease
Current Alzheimer Research Heart Failure Pharmacotherapy: Differences Between Adult and Paediatric Patients
Current Medicinal Chemistry Phenolic Content in Traditionally Processed Erythrina indica L. Seeds: Antioxidant Potential and Type II Diabetes Related Functionality
Current Nutrition & Food Science Biological Therapies: Effects of Proinflammatory Pathways and their Inhibition on the Myocardium of Rheumatoid Athritis Patients
Current Medicinal Chemistry Cardiac SPECT-CT and PET-CT Imaging
Current Medical Imaging Total Lipids and Fatty Acid Methyl Esters of Germinated Seeds of Mangrove Wild Legume
Current Nutrition & Food Science Inflammatory Biomarkers, Depressive Symptoms and Falls Among the elderly in Panama
Current Aging Science Fibrinolytic Therapy in Acute Stroke
Current Cardiology Reviews Advanced Glycation: A Novel Outlook on Atherosclerosis
Current Pharmaceutical Design Peroxisome Proliferator-Activated Receptor γ Agonists as Insulin Sensitizers: From the Discovery to Recent Progress
Current Topics in Medicinal Chemistry Pharmacogenomics of Osteoporosis
Current Pharmacogenomics Expression and Role of the Calcium-Sensing Receptor in the Blood Vessel Wall
Current Pharmaceutical Biotechnology Hyperglycaemia and Vitamin D: A Systematic Overview
Current Diabetes Reviews The Role of Dairy Products in Healthy Weight and Body Composition in Children and Adolescents
Current Nutrition & Food Science Hydrophilic Carotenoid Amphiphiles: Methods of Synthesis and Biological Applications
Mini-Reviews in Medicinal Chemistry Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic Heart Diseases: Similarities and Differences
Current Cardiology Reviews Drug-Induced Hypokalaemia
Current Drug Safety