Abstract
P2X receptors are trimeric ligand-gated ion channels whose potential as novel drug targets for a number of diseases has been recognized. They are mainly involved in inflammatory processes, including neuroinflammation, and pain sensation. The orthosteric binding site is lined by basic amino acid residues that bind the negatively charged agonist ATP. Therefore it is not easy to develop orthosteric ligands that possess drug-like properties for such a highly polar binding site. However, ligand-gated ion channels offer multiple additional binding sites for allosteric ligands, positive or negative allosteric modulators enhancing or blocking receptor function. So far, the P2X3 (and P2X2/3), as well as the P2X7 receptor subtype have been the main focus of drug development efforts. A number of potent and selective allosteric antagonists have been developed to block these receptors. We start to see the development of novel allosteric ligands also for the other P2X receptor subtypes, P2X1, P2X2 and especially P2X4. The times when only poor, non-selective, non-drug-like tools for studying P2X receptor function were available have been overcome. The first clinical studies with allosteric P2X3 and P2X7 antagonists suggest that P2X therapeutics may soon become a reality.
Keywords: Allosteric modulator, antagonist, P2X receptor, P2X1, P2X2, P2X3, P2X4, P2X7.
Current Medicinal Chemistry
Title:Medicinal Chemistry of P2X Receptors: Allosteric Modulators
Volume: 22 Issue: 7
Author(s): Christa E. Muller
Affiliation:
Keywords: Allosteric modulator, antagonist, P2X receptor, P2X1, P2X2, P2X3, P2X4, P2X7.
Abstract: P2X receptors are trimeric ligand-gated ion channels whose potential as novel drug targets for a number of diseases has been recognized. They are mainly involved in inflammatory processes, including neuroinflammation, and pain sensation. The orthosteric binding site is lined by basic amino acid residues that bind the negatively charged agonist ATP. Therefore it is not easy to develop orthosteric ligands that possess drug-like properties for such a highly polar binding site. However, ligand-gated ion channels offer multiple additional binding sites for allosteric ligands, positive or negative allosteric modulators enhancing or blocking receptor function. So far, the P2X3 (and P2X2/3), as well as the P2X7 receptor subtype have been the main focus of drug development efforts. A number of potent and selective allosteric antagonists have been developed to block these receptors. We start to see the development of novel allosteric ligands also for the other P2X receptor subtypes, P2X1, P2X2 and especially P2X4. The times when only poor, non-selective, non-drug-like tools for studying P2X receptor function were available have been overcome. The first clinical studies with allosteric P2X3 and P2X7 antagonists suggest that P2X therapeutics may soon become a reality.
Export Options
About this article
Cite this article as:
Muller E. Christa, Medicinal Chemistry of P2X Receptors: Allosteric Modulators, Current Medicinal Chemistry 2015; 22 (7) . https://dx.doi.org/10.2174/0929867322666141210155610
DOI https://dx.doi.org/10.2174/0929867322666141210155610 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Characteristics of Products of Fibrinogen Origin in the Presence of Anti-
SARS-CoV-2 IgG in the Bloodstream
Reviews on Recent Clinical Trials SAR Analysis of Various Heterocyclic Compounds in Medicinal Chemistry: Recent Updates-Part-II
Current Topics in Medicinal Chemistry MEET THE GUEST EDITOR
Combinatorial Chemistry & High Throughput Screening Regulation of Innate Immune Responses in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Role of Lipid Nanoparticles in COVID-19 in Repurposing Drugs and Vaccines
Current Nanoscience Muscular Gene Transfer Using Nonviral Vectors
Current Gene Therapy A Viewpoint on Potential Biomarkers for Infectious COVID-19 Severity: An Updated Literature Survey
Infectious Disorders - Drug Targets Fatty Acid Biosynthesis: An Updated Review on KAS Inhibitors
Current Drug Discovery Technologies Novel Nicotinonitrile Derivatives Bearing Imino Moieties Enhance Apoptosis and Inhibit Tyrosine Kinase
Anti-Cancer Agents in Medicinal Chemistry Biology and Clinical Management of Myeloproliferative Neoplasms and Development of the JAK Inhibitor Ruxolitinib
Current Medicinal Chemistry Prolyl Peptidases Related to Dipeptidyl Peptidase IV: Potential of Specific Inhibitors in Drug Discovery.
Current Topics in Medicinal Chemistry Looking for New Targets: Simple Coumarins as Antibacterial Agents
Medicinal Chemistry Visualized Analyses of Investigations Upon Mesenchymal Stem/stromal Cell-based Cytotherapy and Underlying Mechanisms for COVID-19 Associated ARDS
Current Stem Cell Research & Therapy The Insights on Why Diabetes Prevalence May Increase Amid or Post COVID-19 Pandemic
Current Diabetes Reviews Molecular Docking, DFT Studies and ADMET Simulations for Evaluating Already Approved FDA Drugs as Inhibitors for SARS-Cov-2 RNADependent Polymerase
Letters in Drug Design & Discovery Selective Activation of Intracellular Signalling Pathways in Dendritic Cells for Cancer Immunotherapy
Anti-Cancer Agents in Medicinal Chemistry Recent Progress on Anti-Liver Fibrosis Candidates in Patents of Herbal Medicinal Products
Recent Patents on Food, Nutrition & Agriculture Preface
Current Topics in Medicinal Chemistry Molecular Mechanisms Regulating mRNA Stability: Physiological and Pathological Significance
Current Genomics Drug-Induced Pulmonary Hypertension in Newborns: A Review.
Current Vascular Pharmacology