Abstract
While estrogen receptor (ER)-targeted therapeutics have clearly been a success in the treatment of breast cancer, the orphan estrogen-related receptors (ERRs) represent novel targets for future development. The ERRs, comprising ERRα, ERRβb and ERRγ, bind and regulate transcription via estrogen response elements (EREs) and extended ERE half-sites termed ERR response elements (ERREs), but do not bind endogenous estrogens. The emerging role of ERRα and ERRγ in modulating estrogen responsiveness, substituting for ER activities, and serving as prognosticators in breast and other cancers is providing an impetus for the identification of compounds which target these proteins. Moreover, ERRα plays a role in energy homeostasis and will likely be targeted for the treatment of metabolic disorders. Multiple classes of synthetic ligands have already been identified. The phytoestrogens genistein, daidzein, biochanin A and 6,34-tryhydroxyflavone have been reported as ERRa agonists. The phenolic acyl hydrazones GSK4716 and GSK9089 act as selective agonists of ERRβ and ERRγ. The organochlorine pesticides toxaphene and chlordane, and the synthetic compound XCT790 antagonize ERRα. The synthetic estrogen diethylstilbestrol antagonizes all three ERRs. The selective estrogen receptor modulators 4-hydroxytamoxifen and 4-hydroxytoremifene antagonize ERRγ. The rational development of synthetic ligands for the ERRs may soon provide new agents to supplement the repertoire of antihormonal therapies to combat breast cancer. Moreover, expression of ERRs in other cancers and metabolic disorders may provide a targeted treatment strategy for these patients as well.
Keywords: Estrogen-related receptor, estrogen responsiveness, breast cancer, ovarian cancer, energy homeostasis
Current Topics in Medicinal Chemistry
Title: Estrogen-Related Receptors as Emerging Targets in Cancer and Metabolic Disorders
Volume: 6 Issue: 3
Author(s): Eric A. Ariazi and V. C. Jordan
Affiliation:
Keywords: Estrogen-related receptor, estrogen responsiveness, breast cancer, ovarian cancer, energy homeostasis
Abstract: While estrogen receptor (ER)-targeted therapeutics have clearly been a success in the treatment of breast cancer, the orphan estrogen-related receptors (ERRs) represent novel targets for future development. The ERRs, comprising ERRα, ERRβb and ERRγ, bind and regulate transcription via estrogen response elements (EREs) and extended ERE half-sites termed ERR response elements (ERREs), but do not bind endogenous estrogens. The emerging role of ERRα and ERRγ in modulating estrogen responsiveness, substituting for ER activities, and serving as prognosticators in breast and other cancers is providing an impetus for the identification of compounds which target these proteins. Moreover, ERRα plays a role in energy homeostasis and will likely be targeted for the treatment of metabolic disorders. Multiple classes of synthetic ligands have already been identified. The phytoestrogens genistein, daidzein, biochanin A and 6,34-tryhydroxyflavone have been reported as ERRa agonists. The phenolic acyl hydrazones GSK4716 and GSK9089 act as selective agonists of ERRβ and ERRγ. The organochlorine pesticides toxaphene and chlordane, and the synthetic compound XCT790 antagonize ERRα. The synthetic estrogen diethylstilbestrol antagonizes all three ERRs. The selective estrogen receptor modulators 4-hydroxytamoxifen and 4-hydroxytoremifene antagonize ERRγ. The rational development of synthetic ligands for the ERRs may soon provide new agents to supplement the repertoire of antihormonal therapies to combat breast cancer. Moreover, expression of ERRs in other cancers and metabolic disorders may provide a targeted treatment strategy for these patients as well.
Export Options
About this article
Cite this article as:
Ariazi A. Eric and Jordan C. V., Estrogen-Related Receptors as Emerging Targets in Cancer and Metabolic Disorders, Current Topics in Medicinal Chemistry 2006; 6 (3) . https://dx.doi.org/10.2174/1568026610606030203
DOI https://dx.doi.org/10.2174/1568026610606030203 |
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
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
- 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
-
Role of microRNA Deregulation in Breast Cancer Cell Chemoresistance and Stemness
Current Medicinal Chemistry Treatment of Psoriasis: A Comprehensive Review of Entire Therapies
Current Drug Safety Vybrant DyeCycle Violet Stain Discriminates Two Different Subsets of CD34+ Cells
Current Stem Cell Research & Therapy Meet Our Editorial Board Member:
Current Drug Targets Synthesis, Antioxidant, Anticancer and Antiviral Activities of Novel Quinoxaline Hydrazone Derivatives and their Acyclic C-Nucleosides
Medicinal Chemistry Chemical Structure Characteristics and Bioactivity of Small Molecule FAK Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Hepcidin: Biological Activity, Analytical Methods in Biological Fluids, Clinical Applications and Antagonists. A Short Review
Current Pharmaceutical Analysis Valproic Acid As Anti-Cancer Drug
Current Pharmaceutical Design Etiological and Biological Aspects of Cigarette Smoking in Rheumatoid Arthritis
Inflammation & Allergy - Drug Targets (Discontinued) Anti-cancer Effects of Curcumin on Head and Neck Cancers
Anti-Cancer Agents in Medicinal Chemistry NF-κ B and Rheumatic Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets The Emerging Importance of DNA Helicases to Stabilize the Replication Fork
Current Genomics Synthesis of 3-phenyl-4-phenylvinyl Benzopyranones and the Corresponding 2,2-dimethyl-benzopyrans with Structural Similarity to Estradiol, as Estrogen Receptor Ligands
Medicinal Chemistry Genes and Proteins Governing the Cellular Sensitivity to HSP90 Inhibitors: A Mechanistic Perspective
Current Cancer Drug Targets Recent Advances in Optical Molecular Imaging and its Applications in Targeted Drug Delivery
Current Drug Targets Recent Insights into COVID-19 in Children and Clinical Recommendations
Current Pediatric Reviews ABC Pumps and Their Role in Active Drug Transport
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: In vivo MRS: Techniques and Applications)
Current Molecular Imaging (Discontinued) Evaluation of In-Vivo Anti-Implantation and In-Vitro Anti-Proliferative Activities of Substituted 3-phenyl-4-phenylvinyl Benzopyranone Derivatives
Letters in Drug Design & Discovery Catechol-O-Methyltransferase (COMT)-Mediated Methylation Metabolism of Endogenous Bioactive Catechols and Modulation by Endobiotics and Xenobiotics: Importance in Pathophysiology and Pathogenesis
Current Drug Metabolism