Abstract
Farnesoid X receptor (FXR, NR1H4), a nuclear receptor (NR) highly expressed in the liver, intestine, kidney, adrenal glands and other cholesterol-rich tissues, functions as the master regulator for bile acid homeostasis. FXR, which regulates the expression of genes encoding proteins involved in cholesterol homeostasis, plays an essential role in regulating cholesterol, lipid, and glucose metabolism. Recently, some FXR agonists are reported to have low selectivity on NRs, which forces the researchers to move their eyes onto the development of FXR antagonists with high selectivity. The development of non-steroidal FXR antagonists with different scaffolds including AGN34, tuberatolides, atractylenolides, andrographolides, GW4064 derivatives and 1,3,4-trisubstitutedpyrazolones, provides us a prospect for the therapy of in ammation, metabolic syndrome, diabetes, cholesterol gallstones, and cancer.
Keywords: Cholestasis, Farnesoid-x-receptor, Non-steroidal antagonist, Pharmacological target.
Graphical Abstract
Current Topics in Medicinal Chemistry
Title:Recent Advances in Non-Steroidal FXR Antagonists Development for Therapeutic Applications
Volume: 14 Issue: 19
Author(s): Huang Huang, Yong Xu, Jin Zhu and Jian Li
Affiliation:
Keywords: Cholestasis, Farnesoid-x-receptor, Non-steroidal antagonist, Pharmacological target.
Abstract: Farnesoid X receptor (FXR, NR1H4), a nuclear receptor (NR) highly expressed in the liver, intestine, kidney, adrenal glands and other cholesterol-rich tissues, functions as the master regulator for bile acid homeostasis. FXR, which regulates the expression of genes encoding proteins involved in cholesterol homeostasis, plays an essential role in regulating cholesterol, lipid, and glucose metabolism. Recently, some FXR agonists are reported to have low selectivity on NRs, which forces the researchers to move their eyes onto the development of FXR antagonists with high selectivity. The development of non-steroidal FXR antagonists with different scaffolds including AGN34, tuberatolides, atractylenolides, andrographolides, GW4064 derivatives and 1,3,4-trisubstitutedpyrazolones, provides us a prospect for the therapy of in ammation, metabolic syndrome, diabetes, cholesterol gallstones, and cancer.
Export Options
About this article
Cite this article as:
Huang Huang, Xu Yong, Zhu Jin and Li Jian, Recent Advances in Non-Steroidal FXR Antagonists Development for Therapeutic Applications, Current Topics in Medicinal Chemistry 2014; 14 (19) . https://dx.doi.org/10.2174/1568026614666141112101840
DOI https://dx.doi.org/10.2174/1568026614666141112101840 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
HIV-1, Methamphetamine and Astrocyte Glutamate Regulation: Combined Excitotoxic Implications for Neuro-AIDS
Current HIV Research Brain Aging and Disorders of the Central Nervous System: Kynurenines and Drug Metabolism
Current Drug Metabolism Functional Null Mutations in the Gonosomal Homologue Gene TBL1Y are Associated with Non-Syndromic Coarctation of the Aorta
Current Molecular Medicine Regulatory T Cells: Major Players in the Tumor Microenvironment
Current Pharmaceutical Design The Role of SHP-2 in Cell Signalling and Human Disease
Current Enzyme Inhibition Phosphotyrosine Phosphatases in Cancer Diagnostic and Treatment
Recent Patents on DNA & Gene Sequences Current Indications for Implantable Cardioverter Defibrillators in Non-Ischemic Cardiomyopathies and Channelopathies
Reviews on Recent Clinical Trials Role of Estradiol and Progesterone in HIV Susceptibility and Disease Progression
Mini-Reviews in Medicinal Chemistry Myelodysplastic/Myeloproliferative Neoplasms
Current Cancer Therapy Reviews Vitamin D and Vitamin D Receptor Activators in Treatment of Hypertension and Cardiovascular Disease
Cardiovascular & Hematological Disorders-Drug Targets Pleiotropic Effects of PPARγ Agonist on Hemostatic Activation in Type 2 Diabetes Mellitus
Current Vascular Pharmacology Beyond Bile Acids: Targeting Farnesoid X Receptor (FXR) with Natural and Synthetic Ligands
Current Topics in Medicinal Chemistry Protein Tyrosine Phosphatases, New Targets for Cancer Therapy
Current Cancer Drug Targets Mining for Protein Kinase Substrates: Integration of Biochemistry, Genetics and Proteomics
Current Proteomics Biomarkers in Post-stroke Depression
Current Neurovascular Research Genetic Predisposition to Neonatal Tumors
Current Pediatric Reviews Previously Apparently Undescribed Autosomal-Recessive Multiple Congenital Anomalies/ Mental Retardation (MCA/MR) Syndrome Comprising: Fronto-Nasal Dysplasia, Hypertelorism, Short Stature and Brachydactily
Current Pediatric Reviews Rational Targeting of Peroxisome Proliferating Activated Receptor Subtypes
Current Medicinal Chemistry The Many Neuroprogressive Actions of Tryptophan Catabolites (TRYCATs) that may be Associated with the Pathophysiology of Neuro-Immune Disorders
Current Pharmaceutical Design Role of Vitamin D in the Pathophysiology and Treatment of Type 2 Diabetes
Current Diabetes Reviews