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The Future of GPCRs in Drug Discovery: Novel Technologies, Leading Companies, and Opportunities for Target Expansion
Date:11/8/2010

aches such as allosteric modulation, bifunctional ligand design, and the targeting of dimeric receptors. Both old and new targets are considered in terms of their potential to offer fresh opportunities, and particular attention is given to the current and future roles of orphan receptors. Finally, the report profiles a range of companies specializing in aspects of GPCR drug discovery, and the market outlook is summarized.

List of TablesThe Future of GPCRs in Drug Discovery

Executive summary 10

Introduction 10

Characteristics of GPCRs 10

Commercial exploitation 11

New approaches 12

New opportunities 13

Specialist company profiles 14

Market outlook for dugs targeting GPCRs 14

Chapter 1 Introduction 18

Summary 18

Introduction 18

GPCRs in the human genome 19

Additional opportunities 20

The leading class of drug targets 21

Commercially validated targets 23

Chapter 2 Characteristics of GPCRs 28

Summary 28

Introduction 28

Protein structure 29

Functional receptors 31

Second messengers 31

Agonists, antagonists, partial agonists, and inverse agonists 33

Chapter 3 Commercial exploitation 36

Summary 36

Introduction 37

Current successes 37

Targeted GPCRs 44

Unexplored targets 47

Difficult targets 50

Opportunities 50

Chapter 4 New approaches 54

Summary 54

Introduction 55

Screening methods 56

Structure-based methods 57

Knowledge-based methods 60

Allosteric modulators 62

Bifunctional ligands 65

Dimeric receptor targeting ligands 66

Biased ligands 68

Chapter 5 New opportunities 72

Summary 72

Introduction 73

Enhanced selectivity 73

Atypical antipsychotics 75

Lorcaserin 78

Adenosine A2A antagonists 79

New targets 80

Ghrelin antagonists 81
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