Abstract
Retinoic acid receptors (RARs) are ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth, differentiation, survival and death. Due to their regulatory potential, these nuclear receptors (NRs) are major drug targets for a variety of pathologies, including cancer and metabolic diseases. A large amount of RAR- and RXR-selective ligands, ranging from (partial) agonists to antagonists and inverse agonists, have been designed and the corresponding structural and functional analyses have provided deep insight into the molecular basis of ligand action. Ligands regulate, via allosteric conformational changes, the ability of these NRs to interact with different sets of coregulators, which in turn recruit enzymatically active complexes/machineries. Here, we describe strategies in the design of selective RXR and RAR modulators and review the structural mechanisms by which the diverse pharmacological classes of compounds modulate receptor functions. Finally, we discuss the perspectives for retinoid- and rexinoid-based therapies.
Keywords: Retinoic acid receptors, retinoid X receptors, agonists and antagonists action, ligand design, selective ligands, structure-function relationship, thee-dimensional structure, therapeutic potential, antagonists rexinoid apoptosis, retinoid- and rexinoid-based therapies
Current Topics in Medicinal Chemistry
Title: Retinoid Receptors and Therapeutic Applications of RAR/RXR Modulators
Volume: 12 Issue: 6
Author(s): Albane le Maire, Susana Alvarez, Pattabhiraman Shankaranarayanan, Angel R de Lera, William Bourguet and Hinrich Gronemeyer
Affiliation:
Keywords: Retinoic acid receptors, retinoid X receptors, agonists and antagonists action, ligand design, selective ligands, structure-function relationship, thee-dimensional structure, therapeutic potential, antagonists rexinoid apoptosis, retinoid- and rexinoid-based therapies
Abstract: Retinoic acid receptors (RARs) are ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth, differentiation, survival and death. Due to their regulatory potential, these nuclear receptors (NRs) are major drug targets for a variety of pathologies, including cancer and metabolic diseases. A large amount of RAR- and RXR-selective ligands, ranging from (partial) agonists to antagonists and inverse agonists, have been designed and the corresponding structural and functional analyses have provided deep insight into the molecular basis of ligand action. Ligands regulate, via allosteric conformational changes, the ability of these NRs to interact with different sets of coregulators, which in turn recruit enzymatically active complexes/machineries. Here, we describe strategies in the design of selective RXR and RAR modulators and review the structural mechanisms by which the diverse pharmacological classes of compounds modulate receptor functions. Finally, we discuss the perspectives for retinoid- and rexinoid-based therapies.
Export Options
About this article
Cite this article as:
le Maire Albane, Alvarez Susana, Shankaranarayanan Pattabhiraman, R de Lera Angel, Bourguet William and Gronemeyer Hinrich, Retinoid Receptors and Therapeutic Applications of RAR/RXR Modulators, Current Topics in Medicinal Chemistry 2012; 12 (6) . https://dx.doi.org/10.2174/156802612799436687
DOI https://dx.doi.org/10.2174/156802612799436687 |
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
-
Stereotactic Body Radiotherapy in the Management of Head and Neck Malignancies
Current Cancer Therapy Reviews miR-629-3p Level Significantly Predicts Prognosis in Glioblastoma Patients Treated with Temozolomide Chemotherapy
Current Signal Transduction Therapy Retinoids as Differentiating Agents in Oncology: A Network of Interactions with Intracellular Pathways as the Basis for Rational Therapeutic Combinations
Current Pharmaceutical Design Advanced Assessment of the Endogenous Hormone Level as a Potential Biomarker of the Urogenital Tract Cancer
Combinatorial Chemistry & High Throughput Screening The Impact of the Theory-Based Training on Beliefs of Women towards Breast Cancer Screening Behaviors
Current Women`s Health Reviews Synthesis of Purine Derivatives as Scaffolds for a Diversity of Biological Activities
Current Organic Chemistry Protective Role of Natural Products in Glioblastoma Multiforme: A Focus on Nitric Oxide Pathway
Current Medicinal Chemistry Experimental Models of Abdominal Aortic Aneurysms: An Overview
Current Pharmaceutical Design Neuroprotective Effects of Non-Classical Estrogen-Like Signaling Activators: from Mechanism to Potential Implications
CNS & Neurological Disorders - Drug Targets Biology of Circulating Nucleic Acids and Possible Roles in Diagnosis and Treatment in Diabetes and Cancer
Infectious Disorders - Drug Targets Current Developments of Coumarin Compounds in Medicinal Chemistry
Current Pharmaceutical Design Chemistry and Pharmacology of Bioactive Molecule -Coenzyme Q10: A Brief Note
Current Bioactive Compounds Synthesis and Biological Evaluation of a Series of 2-(Substitutedphenyl) benzothiazoles
Medicinal Chemistry MicroRNAs: Association with Radioresistant and Potential Uses of Natural Remedies as Green Gene Therapeutic Approaches
Current Gene Therapy Potential Use of Protease Inhibitors as Vaginal and Colorectal Microbicides
Current HIV Research Natural Products and Cancer Stem Cells
Current Pharmaceutical Design Macromolecular Drug Targets in Cancer Treatment and Thiosemicarbazides as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Biomolecules Linked to Transition Metal Complexes - New Chances for Chemotherapy
Current Medicinal Chemistry Molecular Mechanisms and Proposed Targets for Selected Anticancer Gold Compounds
Current Topics in Medicinal Chemistry Interferons: Mechanisms, Biological Activities and Survey of their Use in Human Diseases
Current Bioactive Compounds