Description

G protein coupled receptors remain the most important class of therapeutic targets in medicine. In the last 5 years, tremendous advances have been made in our understanding of the structure and mechanism of this critical family of drug targets. The present volume explores the modern experimental and conceptual framework for drug discovery for G protein coupled receptors. It explores advances in structure determination and structure-based drug design as well as new concepts of allosteric modulation, functional selectivity/biased agonism, and pharmacological chaperones. In addition, emerging drug targets such as receptor families for fatty acids, carboxylic acids, lipid mediators, etc. are included. Final chapters cover novel mechanisms of signal regulation through PDZ domains and RGS proteins. This volume will bring an up-to-date perspective on the G protein coupled receptor field to both academic and industry scientists.

Key Features

The present volume explores the modern experimental and conceptual framework for drug discovery for G protein coupled receptors
It explores advances in structure determination and structure-based drug design as well as new concepts of allosteric modulation, functional selectivity/biased agonism, and pharmacological chaperones
This volume will bring an up-to-date perspective on the G protein coupled receptor field to both academic and industry scientists

Readership

Pharmacologists, immunologists, and biochemists

Table of Contents

Contributors

Preface

The Use of GPCR Structures in Drug Design

Abbreviations

I. Introduction

II. Technology Developments Enabling GPCR Structure Determination

III. GPCR Structures

IV. GPCR Structures in Drug Discovery

V. Conclusion

Acknowledgments

Allosteric Modulation of Metabotropic Glutamate Receptors

Abbreviations

I. Introduction

II. Metabotropic Glutamate Receptors

III. Pharmacological Profiles of mGlu Allosteric Modulators

IV. Quantifying Allosteric Interactions

V. Structural Determinants of mGlu Allosteric Modulator Binding

VI. Functional Selectivity of mGlu Allosteric Modulation

VII. Therapeutic Potential of mGlu Allosteric Modulators

VIII. Conclusion

Acknowledgments

Refining Efficacy

Abbreviations

I. Introduction

II. GPCRs as Conformational Ensembles

III. The Pluridimensional Nature of GPCR Efficacy

IV. Functionally Selective GPCR Agonism

V. Functional Selectivity and Pharmaceutical Development

VI. Functional Selectivity at the Parathyroid Hormone Receptor

VII. Conclusion

Acknowledgments

Pharmacological Chaperones for Misfolded Gonadotropin-Releasing Hormone Receptors

Abbreviations

I. Introduction

II. The Endoplasmic Reticulum Quality Control System

III. Misfolding of GPCRs and Disease

IV. Mutations in the Human GnRHR

V. Rescue of Misfolded hGnRHR Mutants with Pharmacoperones

VI. Mechanism of Action of Pharmacoperones

VII. The Dominant-Negative Effect of hGnRHR Mutants and Receptor Rescue

VIII. Conclusion

Acknowledgments

Regulation of Stability and Trafficking of Calcium-Sensing Receptors by Pharmacologic Chaperones

Abbreviations

I. Introduction

Details

No. of pages:
408
Language:
English
Copyright:
© 2011
Published:
Imprint:
Academic Press
Print ISBN:
9780123859525
Electronic ISBN:
9780123859532