Allosteric Modulation of G Protein-Coupled Receptors

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.

Table of Contents:
Part I: Core Concepts 1. G Protein-Coupled Receptor-Dependent Signal Transduction: Orthosteric and Allosteric Mechanisms 2. Analysis of Allosteric Modulation: Curve-Fitting and Modelling 3. Critical Caveats: Probe-Dependence and Ligand Bias 4. Ions as Allosteric Modulators 5. Small Molecules as Allosteric Modulators 6. Oligomerization: Protein-Protein Allosteric Effects Part II: Critical Advances 7. Crystal Structures of G Protein-Coupled Receptors in Complex with Allosteric Modulators 8. Receptor Subtype Selectivity: Muscarinic Receptors 9. Receptor Subtype Selectivity: Opioid Receptors 10. Lipid-based Allosteric Modulators 11. Moving from Cells to Animals: Challenges of Studying Allosteric Modulators In vivo 12. Disease Targets: Pain 13. Disease Targets: Anxiety 14. New Drug Targets: Clinical Translation of Allosteric Modulators, Cinacalcet Part III: Key Methodologies 15. In silico Analysis of Allosteric Modulators 16. Mapping Structure-Activity Relationships for Allosteric Modulators 17. Kinetic Considerations of Allosteric Modulators 18. Binding and Ligand Affinity 19. Photoaffinity Ligands and the Metabotropic Glutamate Receptors 20. Biosensors for the Study of Allosteric Modulation

About the Author :
Robert Laprairie is the GlaxoSmithKline-Canadian Institutes of Health Research chair in Drug Discovery and Development in the College of Pharmacy and Nutrition at the University of Saskatchewan. He currently serves as the President and Director of Education and Trainee Initiatives for the Canadian Consortium for the Investigation of Cannabinoids (CCIC). His teaching responsibilities include basic molecular pharmacology and neuroscience in the undergraduate and graduate Pharmacy programs. He is also involved in committee work with the Canadian Institutes of Health Research and the Animal Research Ethics Board of the University of Saskatchewan. Dr. Laprairie has published more than 50 articles on pharmacology with a focus on the endocannabinoid system and allosteric modulators.