GPCRs in Drug Discovery - Efforts to De-Orphanize Novel GPCR Targets are Increasing

GPCRs in Drug Discovery - Efforts to De-Orphanize Novel GPCR Targets are Increasing

Summary

GBI Research, the leading business intelligence provider, has released its latest research “GPCRs in Drug Discovery - Efforts to De-Orphanize Novel GPCR Targets are Increasing” which provides insights in to the technical and commercial importance of G protein coupled receptors, which are the most important category of receptors in the human body. The report provides a scientific understanding of GPCRs and details the novel research methods being employed in the research of new targets and molecules that can be more effective in treating many indications. A special note on Orphan GPCRs and ways to de-orphanize them is followed by a detailed pipeline analysis to understand the therapeutic classes and indications that are being targeted through GPCRs. The report provides an in-depth analysis of the competitive landscape, including the profiling of top companies and licensing agreements involving GPCR molecules and platform technologies.

Scope

The scope of this report includes -
- Detailed technical understanding of G protein coupled receptors
- Dedicated sections on Novel research methods being used to improve the GPCR targeted drug discovery and development process
- Understanding of Orphan GPCRs, its importance and novel methods to locate ligands and de-orphanize these receptors
- Pipeline analysis of products at various stages of development targeting receptors classified as GPCRs, including identification of major therapeutic areas and indications
- Analysis and review of important strategic partnerships and licensing agreements in the area of GPCR drug discovery and development
- The report also covers information on the leading market players and the competitive landscape, including specialist companies which have proprietary GPCR platform technology as well as major companies with molecules in not only the NDA Filed stage but also in Phase III

Reasons to buy

The report will enhance your decision making capability. It will allow you to -
- Develop business strategies by understanding the trends shaping and driving research in the field of GPCRs
- Understand the potential areas of application for GPCR therapies.
- Identify key molecules targeting GPCRs in development based on the therapy.
- Identify the key players investing in GPCR platform technologies
- Optimize your R&D pipeline through identification of novel technologies being used in GPCR research to improve the drug discovery process
- Identify emerging players with a potentially strong product portfolio of molecules targeting GPCRs and create effective counter-strategies to gain a competitive advantage.
- What’s the next big thing in GPCR research? – Identify, understand and capitalize. SHOW LESS READ MORE >

1
1 4
1.1 List of Tables 8
1.2 List of Figures 10
2 GPCRs in Drug Discovery – Introduction 12
2.1 GBI Research Report Guidance 12
3 GPCRs in Drug Discovery – Overview 13
3.1 Introduction 13
3.2 GPCR in the Human Genome 14
3.2.1 Introduction 14
3.2.2 The Traditional Classification System 14
3.2.3 The GRAFS Classification System 15
3.3 Structure of GPCRs 17
3.3.1 General Structure 17
3.3.2 Importance of the 7TM 17
3.4 Structure of G-proteins 18
3.5 Coupling to G-proteins 19
3.5.1 Introduction 19
3.5.2 The Signal Transduction Pathways Involving GPCR 19
3.6 Second Messengers in the GPCR System 22
3.6.1 Introduction to Second Messengers 22
3.6.2 Cyclic Adenosine Monophosphate (cAMP) 22
3.6.3 Cyclic Guanosine Monophosphate (cGMP) 23
3.6.4 Diacylglycerol (DAG) 23
3.6.5 Inositol 1, 4, 5-triphosphate (IP3) 24
3.6.6 Calcium Ions (Ca2+ ) 24
3.7 Post-Translational Modifications 25
3.7.1 Glycosylation, Palmitoylation and Phosphorylation 25
3.7.2 GPCR Desensitization 25
4 GPCRs in Drug Discovery – Novel Research Methods in GPCR Drug Discovery 26
4.1 Introduction 26
4.2 Structure-Based Research in GPCR 26
4.2.1 Introduction 26
4.2.2 New Avenues 26
4.2.3 Case Studies 27
4.3 Fragment-Based Drug Discovery 28
4.3.1 Introduction 28
4.3.2 New Avenues 28
4.3.3 Case Study 28
4.4 Ligand-Induced Selective Signaling (LiSS) 28
4.4.1 Introduction 28
4.4.2 New Avenues 29
4.4.3 Case Study 29
4.5 Allosterism and GPCRs 29
4.5.1 Introduction 29
4.5.2 New Avenues 30
4.5.3 Case Studies 31
4.6 GPCR Dimerization 32
4.6.1 Introduction 32
4.6.2 Need to Form Dimers 32
4.6.3 New Avenues 32
4.6.4 Case Studies 33
4.7 GPCR Oligomerization 34
4.7.1 Introduction 34
4.7.2 Classification of Oligomers 34
4.7.3 New Avenues 35
4.7.4 Case Studies 35
5 GPCRs in Drug Discovery – Orphan GPCRs 36
5.1 Introduction 36
5.1.1 Orphan GPCRs in the GRAFS Classification System 36
5.1.2 Orphan GPCRs in the Traditional Classification System 37
5.2 Current Methods Used in De-orphanization 38
5.2.1 Introduction 38
5.2.2 Reverse Pharmacology 39
5.2.3 Orphan Receptor Strategy 40
5.2.4 Phylogenetic Analysis and Chemogenomics 40
5.3 Functional Assays for De-orphanization 40
5.3.1 Introduction 40
5.3.2 G protein-dependent Assays 40
5.3.3 Recent G protein-independent Assays 41
6 GPCRs in Drug Discovery – Pipeline Analysis by Therapeutic Class 42
6.1 Central Nervous System 46
6.1.1 Introduction 46
6.1.2 Pipeline Profile 46
6.1.3 Major Indications 47
6.2 Oncology 52
6.2.1 Introduction 52
6.2.2 Pipeline Profile 52
6.2.3 Major Indications 53
6.3 Cardiovascular System 56
6.3.1 Introduction 56
6.3.2 Pipeline Profile 56
6.3.3 Major Indications 57
6.4 Metabolic Disorders 60
6.4.1 Introduction 60
6.4.2 Pipeline Profile 60
6.4.3 Major Indications 61
6.5 Gastrointestinal Disorders 64
6.5.1 Introduction 64
6.5.2 Pipeline Profile 64
6.5.3 Major Indications 65
6.6 Respiratory Diseases 67
6.6.1 Introduction 67
6.6.2 Pipeline Profile 67
6.6.3 Major Indications 68
6.7 Immunology 71
6.7.1 Introduction 71
6.7.2 Pipeline Profile 71
6.7.3 Major Indications 72
6.8 Women’s Health 74
6.8.1 Introduction 74
6.8.2 Pipeline Profile 74
6.8.3 Major Indications 75
6.9 Ophthalmology 78
6.9.1 Introduction 78
6.9.2 Pipeline Profile 78
6.9.3 Major Indications 79
6.10 Genito-Urinary System and Sex Hormones 82
6.10.1 Introduction 82
6.10.2 Pipeline Profile 82
6.10.3 Major Indications 83
7 GPRCs in Drug Discovery – Pipeline Analysis by Indications 85
7.1 Diabetes 88
7.1.1 Introduction 88
7.1.2 Pipeline Profile 88
7.1.3 Analysis of Major Targets 89
7.2 Parkinson’s Disease 91
7.2.1 Introduction 91
7.2.2 Pipeline Profile 91
7.2.3 Analysis of Major Targets 92
7.3 Pain 94
7.3.1 Introduction 94
7.3.2 Pipeline Profile 94
7.3.3 Analysis of Major Targets 95
7.4 Schizophrenia 97
7.4.1 Introduction 97
7.4.2 Pipeline Profile 97
7.4.3 Analysis of Major Targets 98
7.5 Obesity 100
7.5.1 Introduction 100
7.5.2 Pipeline Profile 100
7.5.3 Analysis of Major Targets 101
7.6 Hypertension 103
7.6.1 Introduction 103
7.6.2 Pipeline Profile 103
7.6.3 Analysis of Major Targets 104
7.7 Asthma 106
7.7.1 Introduction 106
7.7.2 Pipeline Profile 106
7.7.3 Analysis of Major Targets 107
7.8 Prostate Cancer 109
7.8.1 Introduction 109
7.8.2 Pipeline Profile 109
7.8.3 Analysis of Major Targets 110
7.9 Chronic Obstructive Pulmonary Disease (COPD) 112
7.9.1 Introduction 112
7.9.2 Pipeline Profile 112
7.9.3 Analysis of Major Targets 113
7.10 Glaucoma 115
7.10.1 Introduction 115
7.10.2 Pipeline Profile 115
7.10.3 Analysis of Top Targets 116
8 GPCRs in Drug Discovery – Competitive Landscape 118
8.1 GPCRs in Drug Discovery – Major Companies With GPCR Platform Technology 118
8.1.1 Heptares Therapeutics Ltd. 118
8.1.2 Receptos Inc. 118
8.1.3 7TM Pharma A/S 119
8.1.4 Dimerix Biosciences Pvt. Ltd. 119
8.1.5 Trevena, Inc. 119
8.1.6 Cara Therapeutics, Inc. 120
8.1.7 Addex Pharmaceuticals 120
8.1.8 Anchor Therapeutics 121
8.1.9 Domain Therapeutics 121
8.1.10 Euroscreen S.A. 122
8.1.11 Omeros Corporation 122
8.1.12 Arena Pharmaceuticals 123
8.1.13 Compugen, Ltd. 123
8.1.14 Tranzyme Pharma, Inc. 124
8.1.15 Oxagen Limited 125
8.1.16 Prosarix Ltd. 125
8.1.17 Acadia Pharmaceuticals Inc. 126
8.1.18 Actelion Ltd. 127
8.1.19 AcurePharma AB 127
8.1.20 DiscoveRx 127
8.2 GPCRs in Drug Discovery – Top 5 Companies as per Number of Molecules in NDA Filed and in Phase III 128
8.2.1 Merck & Co., Inc. 128
8.2.2 Novartis AG 130
8.2.3 Pfizer Inc. 131
8.2.4 Eli Lilly and Company 132
8.2.5 Johnson and Johnson 133
9 GPCRs in Drug Discovery – Strategic Consolidations 134
9.1 AstraZeneca Enters Into Co-Development Agreement With Heptares 134
9.2 Heptares Therapeutics Enters Into Option Licensing Agreement With Shire For Adenosine A2A 134
9.3 Dimerix Bioscience Enters Into Research Agreement With Takeda Cambridge 135
9.4 Heptares Therapeutics Enters Into Drug Discovery Collaboration With Takeda Pharmaceutical Company Ltd. 135
9.5 ACADIA Pharmaceuticals Extends Drug Discovery Collaboration With Allergan 136
9.6 Omeros Expands Licensing Agreement With Daiichi Sankyo 136
9.7 Domain Therapeutics Enters Into Licensing Agreement With Merck Serono 137
9.8 Receptos Enters Into Collaboration with Eli Lilly 137
9.9 Receptos Enters Into Licensing Agreement With Ortho-McNeil-Janssen Pharmaceuticals 138
9.10 Anchor Therapeutics Enters Into Licensing Agreement with Ortho-McNeil-Janssen 138
10 GPCRs in Drug Discovery – Appendix 139
10.1 Market Definitions 139
10.2 Abbreviations 139
10.3 Research Methodology 139
10.3.1 Coverage 139
10.3.2 Secondary Research 140
10.3.3 Primary Research 140
10.3.4 Expert Panel Validation 140
10.3.5 Section-wise Methodology 141
10.4 Contact Us 143
10.5 Disclaimer 143
10.6 Sources 143

GBI Research’s new report, “GPCRs in Drug Discovery - Efforts to De-Orphanize Novel GPCR Targets are Increasing”, provides insights into the technical and commercial importance of G protein coupled receptors, which are the most important category of receptors in the human body. The report provides a scientific understanding of GPCRs and details the novel research methods being employed in the research of new targets and molecules that can be more effective in treating many indications. A special note on Orphan GPCRs and ways to de-orphanize them is followed by a detailed pipeline analysis to understand the therapeutic classes and indications that are being targeted through GPCRs. The report provides an in-depth analysis of the competitive landscape, including the profiling of top companies and licensing agreements involving GPCR molecules and platform technologies.

G-Protein-Coupled Receptors are the Most Diverse Type of Receptors in the Human Body

GPCRs in Drug Discovery, G Protein-Mediated Signaling of 7TM Receptors

Source: GBI Research, The Scripps Research Institute

A superfamily of diverse transmembrane receptors, GPCRs help in the activation of cellular responses by interacting with molecules outside the cell. These molecules are known as ligands. The cellular responses are activated through a system of signaling pathways, called as signal transduction pathways. Human genome sequencing has helped us to understand the importance of these diverse classes of receptors, with about 1,000 sequences identified to be GPCRs. About 400 GPCRs bind with endogenous ligands; however such ligands have not been discovered for about 33% of all GPCR targets, thus emphasizing on the potential these receptors have as targets for future drug discovery.

Novel Research Methods are Being Employed to Identify and Develop Products that Target GPCRs More Effectively

The understanding of GPCR biology was limited for a very long time, although researchers were successful in identifying many GPCR targets using genomic approaches. However, there was no real understanding of the receptor structure-function relationship, and how different signaling molecules activated these receptors. Hence, the goal was to find the endogenous and/or exogenous ligands that paired with each GPCR, which could help the discovery of new avenues in therapy and de-orphanization of GPCRs. However, there are still more than 100 orphan GPCRs for which ligands have not yet been identified. This coupled with the fact that only about 30% of the 800 odd GPCRs have been targeted so far by currently marketed medicines leads to the conclusion that GPCR research has immense potential to bring out new therapies. Basic research advances concerning receptor X-ray structures, allosteric interactions and functional selectivity have opened the way for further exploitation of this large and diverse class of targets.

Heptares Therapeutics Ltd.
Receptos Inc.
7TM Pharma A/S
Dimerix Biosciences Pvt. Ltd.
Trevena, Inc.
Cara Therapeutics, Inc.
Addex Pharmaceuticals
Anchor Therapeutics
Domain Therapeutics
Euroscreen S.A.
Omeros Corporation
Arena Pharmaceuticals
Compugen, Ltd.
Tranzyme Pharma, Inc.
Oxagen Limited
Prosarix Ltd.
Acadia Pharmaceuticals Inc.
Actelion Ltd.
AcurePharma AB
DiscoveRx
Merck & Co., Inc.
Novartis AG
Pfizer Inc.
Eli Lilly and Company
Johnson and Johnson