Abstract
Since the isolation and identification of the retinoid X receptor (RXR) as a member of the nuclear receptor (NR) superfamily in 1990, its analysis has ushered in a new understanding of physiological regulation by nuclear receptors, and novel methods to identify other unknown and orphan receptors. Expression of one or more of the three isoforms of RXR—α, β, and γ—can be found in every human cell type. Biologically, RXR plays a critical role through its ability to partner with other nuclear receptors. RXR is able to regulate nutrient metabolism by forming “permissive” heterodimers with peroxisome proliferator-activated receptor (PPAR), liver-X-receptor (LXR), farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR), which function when ligands are bound to one or both of the heterodimer partners. Conversely, RXR is able to form “nonpermissive” heterodimers with vitamin D receptor (VDR), thyroid receptor (TR) and retinoic acid receptor (RAR), which function only in the presence of vitamin D, T3 and retinoic acid, respectively. Furthermore, RXR can form homodimers in the presence of a selective agonist, or rexinoid, to regulate gene expression and to either inhibit proliferation or induce apoptosis in human cancers. Thus, over the last 25 years there have been several reports on the design and synthesis of small molecule rexinoids. This review summarizes the synthetic methods for several of the most potent rexinoids thus far reported.
Keywords: Ligand, Organic synthesis, Retinoid, Rexinoid, RXR.
Current Topics in Medicinal Chemistry
Title:Retinoid X Receptor Selective Agonists and their Synthetic Methods
Volume: 17 Issue: 6
Author(s): Carl E. Wagner, Peter W. Jurutka, Pamela A. Marshall and Michael C. Heck
Affiliation:
Keywords: Ligand, Organic synthesis, Retinoid, Rexinoid, RXR.
Abstract: Since the isolation and identification of the retinoid X receptor (RXR) as a member of the nuclear receptor (NR) superfamily in 1990, its analysis has ushered in a new understanding of physiological regulation by nuclear receptors, and novel methods to identify other unknown and orphan receptors. Expression of one or more of the three isoforms of RXR—α, β, and γ—can be found in every human cell type. Biologically, RXR plays a critical role through its ability to partner with other nuclear receptors. RXR is able to regulate nutrient metabolism by forming “permissive” heterodimers with peroxisome proliferator-activated receptor (PPAR), liver-X-receptor (LXR), farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR), which function when ligands are bound to one or both of the heterodimer partners. Conversely, RXR is able to form “nonpermissive” heterodimers with vitamin D receptor (VDR), thyroid receptor (TR) and retinoic acid receptor (RAR), which function only in the presence of vitamin D, T3 and retinoic acid, respectively. Furthermore, RXR can form homodimers in the presence of a selective agonist, or rexinoid, to regulate gene expression and to either inhibit proliferation or induce apoptosis in human cancers. Thus, over the last 25 years there have been several reports on the design and synthesis of small molecule rexinoids. This review summarizes the synthetic methods for several of the most potent rexinoids thus far reported.
Export Options
About this article
Cite this article as:
Wagner E. Carl, Jurutka W. Peter, Marshall A. Pamela and Heck C. Michael, Retinoid X Receptor Selective Agonists and their Synthetic Methods, Current Topics in Medicinal Chemistry 2017; 17 (6) . https://dx.doi.org/10.2174/1568026616666160617091559
DOI https://dx.doi.org/10.2174/1568026616666160617091559 |
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
-
Network Pharmacology-based Prediction and Verification of Shikonin for Treating Colorectal Cancer
Recent Patents on Anti-Cancer Drug Discovery Recent Design and Structure-Activity Relationship Studies on the Modifications of DHFR Inhibitors as Anticancer Agents
Current Medicinal Chemistry Insights Into the Role of microRNAs in Cardiac Diseases: From Biological Signalling to Therapeutic Targets
Cardiovascular & Hematological Agents in Medicinal Chemistry A Progressive Review of V600E-B-RAF-Dependent Melanoma and Drugs Inhibiting It
Mini-Reviews in Medicinal Chemistry Medical Expert Systems
Current Bioinformatics Targeting Histone Onco- Modifications Using Plant-Derived Products
Current Drug Targets Nanotechnology and Radiopharmaceuticals: Diagnostic and Therapeutic Approaches
Current Drug Delivery TNF Superfamily Protein-Protein Interactions: Feasibility of Small- Molecule Modulation
Current Drug Targets Leptin and the Cardiovascular System: A Review
Recent Patents on Cardiovascular Drug Discovery HPLC Analysis of Human Pituitary Hormones for Pharmaceutical Applications
Current Pharmaceutical Analysis The Role of Anti-Inflammatory Drugs in Respiratory Diseases - Pirfenidone, Penicillamine, Chloroquine and Chlorambucil
Current Respiratory Medicine Reviews Positron Emission Tomography Radiopharmaceuticals for Sex Steroid Hormone Receptor Imaging
Current Medicinal Chemistry Functional Evaluation of Neural Stem Cell Differentiation by Single Cell Calcium Imaging
Current Stem Cell Research & Therapy KRAS Mutation Testing of Colorectal Cancer for Anti-EGFR Therapy: Dogmas Versus Evidence
Current Cancer Drug Targets Advances in Hydrogels Applied to Degenerative Diseases
Current Pharmaceutical Design Incretins Yesterday, Pleiotropic Gastrointestinal Hormones Today:Glucagon-Like Peptide-1 (GLP-1) and Glucose-ependent Insulinotropic Polypeptide (GIP)
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Experience with Indium-111 and Yttrium-90-Labeled Somatostatin Analogs
Current Pharmaceutical Design Anticancer Activity of the Bioreductive and Non-Bioreductive Zerumbone Derivatives
Letters in Drug Design & Discovery Anticancer Activity of Organogallium(III) Complexes in Colon Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Structure-Based Approach for the Discovery of Novel Selective Estrogen Receptor Modulators
Current Medicinal Chemistry