Abstract
The nuclear bile acid sensor farnesoid X receptor (FXR) constitutes a rising target for the treatment of a variety of diseases including metabolic disorders, inflammation and certain forms of cancer. While the research on FXR agonists has yielded many compounds and first clinical candidates, only few FXR antagonists have been discovered so far and the knowledge about their in vivo effects is quite narrow. We have evaluated available in vitro and in vivo studies with FXR antagonists as well as FXR knockout models to elucidate a potential pharmacological use of FXR antagonism. To date, the in vitro and in vivo data suggests that FXR inhibition by knockout or the use of antagonists causes beneficial effects on cholesterol metabolism, ameliorates liver toxicity in cholestasis and can reduce the proliferation and migration of some cancer cell lines. Unfortunately, also many disadvantageous effects are connected with FXR antagonists.
Keywords: Atherosclerosis, cancer, FXR antagonists, FXR knockout, glucose homeostasis, guggulsterone, lipid homeostasis, liver disorders, metabolic disorders, selective bile acid receptor modulators (SBARMs).
Current Topics in Medicinal Chemistry
Title:Medicinal Chemistry and Pharmacological Effects of Farnesoid X Receptor (FXR) Antagonists
Volume: 14 Issue: 19
Author(s): Christina Lamers, Manfred Schubert-Zsilavecz and Daniel Merk
Affiliation:
Keywords: Atherosclerosis, cancer, FXR antagonists, FXR knockout, glucose homeostasis, guggulsterone, lipid homeostasis, liver disorders, metabolic disorders, selective bile acid receptor modulators (SBARMs).
Abstract: The nuclear bile acid sensor farnesoid X receptor (FXR) constitutes a rising target for the treatment of a variety of diseases including metabolic disorders, inflammation and certain forms of cancer. While the research on FXR agonists has yielded many compounds and first clinical candidates, only few FXR antagonists have been discovered so far and the knowledge about their in vivo effects is quite narrow. We have evaluated available in vitro and in vivo studies with FXR antagonists as well as FXR knockout models to elucidate a potential pharmacological use of FXR antagonism. To date, the in vitro and in vivo data suggests that FXR inhibition by knockout or the use of antagonists causes beneficial effects on cholesterol metabolism, ameliorates liver toxicity in cholestasis and can reduce the proliferation and migration of some cancer cell lines. Unfortunately, also many disadvantageous effects are connected with FXR antagonists.
Export Options
About this article
Cite this article as:
Lamers Christina, Schubert-Zsilavecz Manfred and Merk Daniel, Medicinal Chemistry and Pharmacological Effects of Farnesoid X Receptor (FXR) Antagonists, Current Topics in Medicinal Chemistry 2014; 14 (19) . https://dx.doi.org/10.2174/1568026614666141112103516
DOI https://dx.doi.org/10.2174/1568026614666141112103516 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
Review of PI3K/mTOR Inhibitors Entering Clinical Trials to Treat Triple Negative Breast Cancers
Recent Patents on Anti-Cancer Drug Discovery Mast Cells as Target in Cancer Therapy
Current Pharmaceutical Design Episomal Lentiviral Vector-Mediated miR-145 Overexpression Inhibits Proliferation and Induces Apoptosis of Human Esophageal Carcinomas Cells
Recent Patents on Anti-Cancer Drug Discovery Advances in Photodynamic Therapy of Cancer
Current Cancer Therapy Reviews Eicosanoids in Prevention and Management of Diseases
Current Molecular Medicine Molecular Components of Wnt/β-catenin Pathway As Therapeutic Targets For Upper Gastrointestinal Cancers
Clinical Cancer Drugs The Synergistic Cytotoxic and Apoptotic Effect of Resveratrol and Naringenin on Y79 Retinoblastoma Cell Line
Anti-Cancer Agents in Medicinal Chemistry MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links
Combinatorial Chemistry & High Throughput Screening Is there Any Correlation Between Binding and Functional Effects at the Translocator Protein (TSPO) (18 kDa)?
Current Molecular Medicine Meet Our Editorial Board Member
Protein & Peptide Letters Reviewing the Cardiovascular Complications of HIV Infection After the Introduction of Highly Active Antiretroviral Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders To Be-et, or Not to Be-et, That is the Question: The Role(s) of Nitrate and Nitrite in Health and Illness
Reviews on Recent Clinical Trials The Renin-angiotensin System as a Target of Novel Anticancer Therapy
Current Pharmaceutical Design Ghrelin and Motilin in the Gastrointestinal System
Current Pharmaceutical Design Transcriptionally Targeted Adenovirus Vectors
Current Gene Therapy The Potential Role of Pharmacogenomic and Genomic in the Adjuvant Treatment of Early Stage Non Small Cell Lung Cancer
Current Genomics Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non-Alcoholic Substances
Current Molecular Pharmacology An Overview on the Role of miR-451 in Lung Cancer: Diagnosis, Therapy, and Prognosis
MicroRNA Inventions Designed to Enhance Drug Delivery Across Epithelial and Endothelial Cells Through the Paracellular Pathway
Recent Patents on Drug Delivery & Formulation Role of Polysaccharides Mimetic Components in Targeted Cancer Treatment
Current Drug Targets