GPCRs: Dawn of a New Era?

Author: Ken Rubenstein, PhD

Chapter 1
INTRODUCTION: THE UNTAPPED PHARMACOLOGIC POTENTIAL OF GPCRS
1.1. Research Advances Stimulating GPCR-Based Drug Discovery
1.2. Goals and Organization of Report

Chapter 2
SCIENTIFIC BACKGROUND AND TECHNOLOGIES
2.1. Nature of GPCRs
GPCRs as Drug Targets
GPCR Classification
2.2. Compound Selection
Functional Assays for GPCR Signaling
      Calcium Assays
      Cellular Dielectric Spectroscopy
      Beta-Arrestin Assays
Structure-Based Drug Discovery

Chapter 3
GPCR PHARMACOLOGY: KEY ADVANCES IN BASIC RESEARCH
3.1. Significance of GPCR Structures
X-Ray Crystallographic Structure of the Beta2-Adrenergic Receptor…Solved
Implications for Structure-Based Drug Design for GPCRs
3.2. Deorphanization
3.3. Allosteric Modulators
3.4. Dimers and Oligomers
3.5. Functional Selectivity

Chapter 4
APPLIED RESEARCH
4.1. Small Companies Push the Limits of GPCR Pharmacology
7TM Pharma
Acadia Pharmaceuticals
Actelion
AcurePharma
Addex Pharmaceuticals
Adenosine Therapeutics (Acquired by Clinical Data)
Arena Pharmaceuticals
Cara Therapeutics
Dimerix Bioscience
EPIX Pharmaceuticals
Trevena
4.2. The GPCR Pipeline
Serotonin Receptors
      5-HT1 Receptor
      5-HT2 Receptor
      5-HT4 to 5-HT7 Receptors
Adenosine Receptors
      A1 Receptor
      A2 and A3 Receptors
Adrenergic Receptors
      Alpha Adrenergic Receptor
      Beta Adrenergic Receptor
Angiotensin II Receptor
Arginine Vasopressin Receptor
Bradykinin Receptors
Calcitonin Receptors
Cannabinoid Receptor
Chemokine Receptors
Cholecystokinin Receptor
Muscarinic Acetylcholine Receptor
Coagulation Factor II Receptor
Corticotropin-Releasing Hormone Receptor 1
Dopamine Receptors
Endothelin Receptor Type A
GABAB Receptor
Glucagon Receptor Family
Metabotropic Glutamate Receptors
Gonadotropin-Releasing Hormone Receptor
Ghrelin Receptor
Histamine Receptor
Interleukin 8 Receptor
Melanin-Concentrating Hormone Receptor 1
Melanocortin Receptor
Motilin Receptor
Opiate Receptor-Like 1 and Opioid Receptors
Oxytocin Receptor
Prostaglandin Receptors
GPCR44
Purinergic P2Y Receptors
Sphingosine-1-Phosphate Receptor 1
Tachykinin Receptors
Additional GPCR Modulators

Chapter 5
DEALS, OBSERVATIONS, AND CONCLUSIONS
5.1. Selected GPCR-Related Deals
5.2. Strengths and Weaknesses of GPCRs as a Target Class
Strengths
Weaknesses
5.3. General Observations and Findings
Diversity of GPCRs for Drug Discovery and Development
Translation of Basic Research and New Technologies
Functional Versus Ligand-Binding Screening Assays
      Cell Impedance Screening Technology
Role of Allostery in Drug Discovery and Development
Role of Dimers and Oligomers in Drug Discovery and Development
Relationship of Signaling Pathway to Disease
Deorphanization and Unfamiliar GPCRs
Structure-Based Drug Design
5.4. Conclusions

Chapter 6
EXPERT INTERVIEWS
6.1. Annette Gilchrist, PhD
Adjunct Professor; Northwestern University
6.2. Graeme Milligan, PhD
Professor of Molecular Pharmacology; Joint Research Director, Faculty of Biomedical and Life Sciences; University of Glasgow
6.3. Anonymous
Screening and Profiling Director; Major Pharmaceutical Company X
6.4. P. Jeffrey Conn, PhD
Lee E. Limbird Professor of Pharmacology; Director, Vanderbilt Program in Drug Discovery; Vanderbilt University Medical Center
6.5. Sidney Topiol, PhD
Associate Director, Computational Chemistry; Lundbeck Research
6.6. Vincent Mutel, PhD
CEO, Vice Chairman, and Co-Founder; Addex Pharmaceuticals

References
Company Index with Web Addresses