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
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...read more
![](/images/wayfinder.jpg)
- 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
-
Therapeutic Challenges in Neuroendocrine Tumors
Anti-Cancer Agents in Medicinal Chemistry Molecular Basis for Designing Selective Modulators of Retinoic Acid Receptor Transcriptional Activities
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Pretargeted Radioimmunotherapy with α-Particle Emitting Radionuclides
Current Radiopharmaceuticals Meet the Editorial Board Member
Current Drug Metabolism Chemokine Receptors as Targets for Cancer Therapy
Current Pharmaceutical Design Targeted Therapies in Solid Tumours: Pinpointing the Tumours Achilles Heel
Current Pharmaceutical Design Molecular Characteristics of Autoimmune Pancreatitis
Current Pharmaceutical Design The Impact of Polycystic Ovary Syndrome (PCOS) on the Risk of Developing Ovarian Cancer and Thyroid Disorders: A Comprehensive Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Treatment of Patients with Advanced Thyroid Cancer
Current Biomarkers (Discontinued) Investigating the In Vivo Expression Patterns of miR-7 microRNA Family Members in the Adult Mouse Brain
MicroRNA Immunomodulatory Effects of Combined Nicotinic Acid and Prednisolone in Adjuvant-induced Arthritis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Chemokines as Pharmacological Targets
Mini-Reviews in Medicinal Chemistry Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention
Current Topics in Medicinal Chemistry A Review on the Use of Statins and Tocotrienols, Individually or in Combination for the Treatment of Osteoporosis
Current Drug Targets Involvement of Metabolites and Non-coding RNAs in Diseases
Current Pharmaceutical Biotechnology Has Selenium a Chemopreventive Effect on Hepatocellular Carcinoma?
Mini-Reviews in Medicinal Chemistry The Potential Health Benefits of Algae and Micro Algae in Medicine: A Review on Spirulina platensis
Current Nutrition & Food Science The Importance of TLR3 Expression and Hormonal Regulation of TLR3- Induced Immune Responses in the Human Endometrium
Current Immunology Reviews (Discontinued) Preclinical Toxicity of Paclitaxel Biopolymer Formulation
Anti-Cancer Agents in Medicinal Chemistry Volatilome Metabolomics and Databases, Recent Advances and Needs
Current Metabolomics