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Transmembrane Transporters: High Sales, High Potential as Drug Targets

Published by: Drug and Market Development Publishing

Published: Jun. 1, 2006 - 312 Pages


Table of Contents


Chapter 1: Executive Summary




Chapter 2: Why Target Transporters?

Introduction

Functions of Transporters

Transport Mechanisms

TC Classification System for Transporters


Transporter Families and Superfamilies


Progress in Structure Elucidation

Top-Selling Transporter-Targeted Drugs




Chapter 3: Ion Transporters

Introduction

Ion Pumps


Overview

Ion Pumps As Drug Targets


The ABC Superfamily

The P-ATPase Superfamily



Ion Channels


Overview


Structural Architectures

Screening Technologies


Sodium Channels As Drug Targets


The Voltage-gated Ion Channel Superfamily

Other Voltage-gated Channels

The Epithelial Na+ Channel Family


Potassium Channels As Drug Targets


The Voltage-gated Ion Channel Superfamily

The Inward Rectifier K+ Channel Family

The Ca2+-activated Auxiliary Subunit Slo â Family


Calcium Channels As Drug Targets


The Voltage-gated Ion Channel Superfamily

Other Calcium Channels


Chloride Channels As Drug Targets


The Epithelial Chloride Channel Family

The Chloride Channel Family



Solute (Ion) Carriers


Overview

Solute Carriers As Drug Targets


The Cation-Chloride Cotransporter Family

The Major Facilitator Superfamily

The Cation:Proton Antiporter1 Family

Other Solute Carriers



Miscellaneous Targets




Chapter 4: Neurotransmitter-binding Transporters

Introduction


Major Neurotransmitters and Their Functions

Role of Membrane Transporters in Neurotransmission


Ionotropic Receptors as Drug Targets


Overview

The Ligand-gated Ion Channel Family


GABA-A Receptors

5-HT3 Receptor

Nicotinic Acetylcholine Receptor

Glycine Receptor


The Glutamate-gated Ion Channel Family


NMDA Receptor

AMPA Receptor

Kainate Receptor


The ATP-gated Cation Channel Family


Solute Carriers as Drug Targets


Overview

The Neurotransmitter:Sodium Symporter Family


Serotonin Transporter

Noradrenalin Transporter

Dopamine Transporter

GABA Transporters

Glycine Transporter


The Dicarboxylate/Amino Acid:Cation Symporter Family

The Major Facilitator Superfamily




Chapter 5: Lipid, Bile Acid, and Carbohydrate Transporters

Lipid and Bile Acid Transporters as Drug Targets


Introduction

The ABC Superfamily


ABCA1 Transporter

ABCG5 and ABCG8 Transporters


The Bile Acid:Na+ Symporter Family


IBAT Transporter


The Putative Fatty Acid Transporter Family


FATP4 Transporter



Carbohydrate Transporters as Drug Targets


Introduction

The Major Facilitator Superfamily


GLUT4 Transporter


The Solute:Sodium Symporter Family


SGLT1 and SGLT2 Transporters





Chapter 6: Other Areas of Research

Transporters in Cancer Drug Resistance


Role of MDR-ABC Transporters


MDR1 Transporter

MRP1 Transporter

MXR Transporter

Other Transporters


Pharmacological Modulation of MDR Transporters


Transporters in ADME/Tox


ABC Transporter Assays for ADME/Tox Prediction

Ion Channel Assays For Cardiac Toxicity


Transporters in Infectious Diseases

Transporters in Drug Delivery




Chapter 7: Market Considerations and Forecasts

Introduction

The Survey


Preliminary Remarks

Questions and Answers

Conclusions


The World Pharmaceutical Market

The Market for Transporter-Targeted Products


Cardiovascular Market

Central Nervous System (CNS) Market

Alimentary/Metabolic Market


Transporter Drug R&D: Leading Indications

Transporter Drug R&D: Leading Companies

Transporter Drug Companies and Applications

Transporter Drug Companies and Targets

Transporter Market Analysis and Forecasts to 2010




Chapter 8: Trends and Opportunities

Transporters Embraced by Big Pharma

Over 100 Transporter Targets Under Investigation

The Most Popular Targets and Indications

Opportunities in Analgesia

Next-Generation Ion Channel Modulators

Next-Generation Ligand-Gated Ion Channel Modulators

Next-Generation Neurotransmitter Re-uptake Inhibitors

Next-Generation Glutamate-Gated Ion Channel Modulators

Exploring New Transporter Targets

Towards Gene Family-Based Transporter Drug Discovery

Expanding Applications Outside Drug Discovery




Chapter 9: Company Profiles

Abbott

Akzo Nobel

Astellas Pharma Inc

AstraZeneca

Bayer AG

Biovail

Boehringer Ingelheim GmbH

Bristol-Myers Squibb

Cortex Pharmaceuticals Inc

Daiichi Sankyo Co Ltd

Elan Plc

Eli Lilly and Company

GlaxoSmithKline Plc

Hoffman-La Roche

ICagen Inc

Johnson & Johnson

Lundbeck A/S

Merck KGaA

Merck & Co Inc

Mitsubishi Pharma

NeuroSearch A/S

Novartis AG

Novo Nordisk A/S

NPS Pharmaceuticals

Pfizer Inc

Sanofi-Aventis

Sepracor Inc

Servier

Takeda Pharmaceutical Company Ltd

Wyeth




Table Of Exhibits

2.1 Transport Mechanisms During the 1990s

2.2 Transporter Classes

2.3 TC Superfamilies

2.4 Targets of Top 100 Drugs by US Sales in 2004

2.5 Top 10 Drugs for 2004 Ranked by US Sales

2.6 Top 10 Drugs for 2004 Ranked by US Sales Growth Rates

2.7 Top-selling Transporter-targeted Drugs for 2004 by US Sales

2.8 Leading Transporter Companies by US Top 100 Sales in 2003 and 2004

3.1 Ion Transporters: Summary of Drug Targets

3.2 Drugs Targeting ATP-Binding Cassette Transporters (ABC Transporters)

3.3 Drugs Targeting ATPases

3.4 Drugs Targeting Sodium Channels (SCNs)

3.5 Drugs Targeting Potassium Channels (KCNs)

3.6 Drugs Targeting Calcium Channels (CACNs)

3.7 Drugs Targeting Chloride Channels

3.8 Drugs Targeting Solute Carriers (SLCs)

3.9 Drugs Targeting Other Transporter Targets

4.1 Neurotransmitter-Binding Transporters: Summary of Drug Targets

4.2 Drugs Targeting Ionotropic Receptors

4.3 Drugs Targeting Solute Carriers (SLCs)

5.1 Lipid, Bile Acid, and Carbohydrate Transporters: Summary of Drug Targets

5.2 Drugs Targeting Lipid, Bile Acid, and Carbohydrate Transporters

7.1 Job Functions of Survey Respondents

7.2 Target Classes by Commercial Potential

7.3 Transporter Target Subclasses by Commercial Potential

7.4 Transporters: Toxicology versus Therapeutics

7.5 Respondents Developing Transporter Drugs

7.6 Transporter Indications in Development

7.7 Transporter Subclasses in Development

7.8 Respondents Marketing Transporter-Targeted Drugs

7.9 Indications of Marketed Transporter-Targeted Drugs

7.10 Targets of Marketed Transporter Drugs

7.11 High-Potential Transporter Indications

7.12 Target Acquisition Strategies

7.13 Target Development Strategies

7.14 World Pharma Market by Region in 2005 and 2010

7.15 World Pharma Market by Indication in 2005 and 2010

7.16 Transporter Drug Indications by Development Stage

7.17 Transporter Companies by Product Portfolio

7.18 Transporter Indications by Top 20 Companies

7.19 Top Transporter Companies by Top Targets

7.20 Top Transporter Indications by Target

7.21 Transporter Market Forecasts by Indication, 2005-2010

7.22 Transporter Market Forecasts by Region, 2005-2010

9.1 Product Portfolio for Abbott by Target

9.2 Product Portfolio for Akzo Nobel by Target

9.3 Product Portfolio for Astellas by Target

9.4 Product Portfolio for AstraZeneca by Target

9.5 Product Portfolio for Bayer by Target

9.6 Product Portfolio for Biovail by Target

9.7 Product Portfolio for Boehringer Ingelheim by Target

9.8 Product Portfolio for Bristol-Myers Squibb by Target

9.9 Product Portfolio for Cortex Pharmaceuticals by Target

9.10 Product Portfolio for Daiichi Sankyo by Target

9.11 Product Portfolio for Elan by Target

9.12 Product Portfolio for Eli Lilly by Target

9.13 Product Portfolio for GlaxoSmithKline by Target

9.14 Product Portfolio for Hoffmann-La Roche by Target

9.15 Product Portfolio for Icagen by Target

9.16 Product Portfolio for Johnson & Johnson by Target

9.17 Product Portfolio for Lundbeck by Target

9.18 Product Portfolio for Merck KGaA by Target

9.19 Product Portfolio for Merck & Co by Target

9.20 Product Portfolio for Mitsubishi Pharma by Target

9.21 Product Portfolio for NeuroSearch by Target

9.22 Product Portfolio for Novartis by Target

9.23 Product Portfolio for Novo Nordisk by Target

9.24 Product Portfolio for NPS Pharmaceuticals by Target

9.25 Product Portfolio for Pfizer by Target

9.26 Product Portfolio for Sanofi-Aventis by Target

9.27 Product Portfolio for Sepracor by Target

9.28 Product Portfolio for Servier by Target

9.29 Product Portfolio for Takeda by Target

9.30 Product Portfolio for Wyeth by Target

Abstract

D&MD’s Transmembrane Transporters: High Sales, High Potential as Drug Targets market report comprehensively reviews transmembrane transporters (including ion channels) and assesses their importance as drug targets. Data presented in this report demonstrates that among the top 100 best-selling drugs in the United States in 2004, transporters represent the most abundant class of targets. This report will help readers assess or reassess their strategies with respect to this target class. An online survey conducted specially for this report shows that transporters (alongside protein kinases), are regarded as commercially the most promising targets available to the drug industry. Although much has been learned about transporters as drug targets, only recently have scientists been able to directly examine three-dimensional ion channel and other integral membrane transporter structures.

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