Allosteric Modulation of G Protein-Coupled Receptors reviews fundamental information on G protein-coupled receptors (GPCRs) and allosteric modulation, presenting original research in the area and collectively providing a comprehensive description of key issues in GPCR allosteric modulation. The book provides background on core concepts of molecular pharmacology while also introducing the most important advances and studies in the area. It also discusses key methodologies. This is an essential book for researchers and advanced students engaged in pharmacology, toxicology and pharmaceutical sciences training and research. Many of the GPCR-targeted drugs released in the past decade have specifically worked via allosteric mechanisms. Unlike direct orthosteric-acting compounds that occupy a similar receptor site to that of endogenous ligands, allosteric modulators alter GPCR-dependent signaling at a site apart from the endogenous ligand. Recent methodological and analytical advances have greatly improved our ability to understand the signaling mechanisms of GPCRs. We now know that allostery is a common regulatory mechanism for all GPCRs and not - as we once believed - unique to a few receptor subfamilies. Introduces background on core concepts of molecular pharmacology, including statistical analyses, non-linear regression, complex models and GPCR-dependent signal transduction as they relate to allosteric modulation Discusses critical advances and landmark studies, including discoveries in the area of GPCR allosteric modulation, which are reviewed for their importance in positive and negative regulation, protein-protein interactions, and small molecule drug discovery Includes key methodologies used to study allosteric modulation at the in silico, in vitro, and in vivo levels of drug discovery and characterization INDICE: Part I: Core Concepts1. G Protein-Coupled Receptor-Dependent Signal Transduction: Orthosteric and Allosteric Mechanisms2. Analysis of Allosteric Modulation: Curve-Fitting and Modelling3. Critical Caveats: Probe-Dependence and Ligand Bias4. Ions as Allosteric Modulators5. Small Molecules as Allosteric Modulators6. Oligomerization: Protein-Protein Allosteric EffectsPart II: Critical Advances7. Crystal Structures of G Protein-Coupled Receptors in Complex with Allosteric Modulators8. Receptor Subtype Selectivity: Muscarinic Receptors9. Receptor Subtype Selectivity: Opioid Receptors10. Lipid-based Allosteric Modulators11. Moving from Cells to Animals: Challenges of Studying Allosteric Modulators In vivo12. Disease Targets: Pain13. Disease Targets: Anxiety14. New Drug Targets: Clinical Translation of Allosteric Modulators, Cinacalcet Part III: Key Methodologies15. In silico Analysis of Allosteric Modulators16. Mapping Structure-Activity Relationships for Allosteric Modulators17. Kinetic Considerations of Allosteric Modulators18. Binding and Ligand Affinity19. Photoaffinity Ligands and the Metabotropic Glutamate Receptors20. Biosensors for the Study of Allosteric Modulation
- ISBN: 978-0-12-819771-4
- Editorial: Academic Press
- Encuadernacion: Rústica
- Páginas: 212
- Fecha Publicación: 10/02/2022
- Nº Volúmenes: 1
- Idioma: Inglés