Innovations in Protein Kinase Therapies: Company pipelines, therapeutic applications and market forecasts

Published by: Business Insights

Published: May. 1, 2009 - 336 Pages

Table of Contents

Kinases: Highways to Drug Discovery Executive Summary

Chapter 1 Kinases as drug targets

Chapter 2 Small molecule kinase inhibitor discovery

Chapter 3 Targeting kinases in cancer

Chapter 4 Non-cancer applications of kinase drugs

Chapter 5 Leading kinase drug originating companies

Chapter 6 Market Analysis: Trends and Forecasts

Chapter 1 Kinases as drug targets

Summary

Introduction

Overview of human protein kinases

Classification schemes

Kinases in signal transduction pathways

MAPK pathways

MAPK (ERK) pathway

JNK/SAPK pathway

MAPK14 pathway

PI3K/AKT signaling

JAK/STAT signaling

NFKB pathway

Insulin receptor signaling

Immune cell signaling

T cell receptor signaling

B-cell receptor complexes

Signaling in vascular morphogenesis

VEGF receptor signaling

EGF receptor signaling

Cyclic nucleotide metabolism

Cell cycle checkpoint controls

Categories of kinase-targeted drugs

Small molecules

Monoclonal antibodies

Emerging biopharmaceuticals

Kinase drug audit

Chapter 2 Small molecule kinase inhibitor discovery

Summary

Introduction

Mechanisms of kinase inhibition

ATP competitive inhibitors

Irreversible inhibitors

Allosteric inhibitors

Approaches to kinase inhibitor discovery

Traditional kinase inhibitor discovery

High-throughput screening of compound libraries

Lead optimization

Synthesis of inhibitor analogs

Structure-informed drug design

Structure-informed drug re-design

Fragment-based drug discovery

Kinase inhibitor selectivity assays

Protein selectivity assays

Kinase activity assays

Kinase binding assays

Cellular selectivity assays

Identifying substrates of kinases

Chapter 3 Targeting kinases in cancer

Summary

Overview of cancer

Established and emerging therapies

Therapeutic potential of kinase inhibition

Types of kinase targets

Mutationally-activated kinases

Kinases which sustain tumor growth

Kinases with roles in tumorigenesis

Top 20 kinase targets

Group: TK

ABL1 (Abl family)

Target characteristics

Inhibitors on the market

Inhibitors in development

EGFR and ERBB2 (EGFR family)

Target characteristics

Approaches to EGFR inhibition

Inhibitors on the market

Inhibitors in development

FLT3, KIT, PDGFRA, and PDGFRB (PDGFR family)

Target characteristics

Inhibitors on the market

Inhibitors in development

FLT1, FLT4, and KDR (VEGFR family)

Target characteristics

Inhibitors on the market

Inhibitors in development

JAK2 (JakA family)

Target characteristics

Drugs in development

MET (Met family)

Target characteristics

Agents in development

Group: AGC

AKT1 (AKT family)

Target characteristics

Drugs in development

Group: CMGC

CDC2 and CDK2 (CDK family; CDC2 subfamily)

Target characteristics

Drugs in development

Group: Other

AURKA and AURKB (AUR family)

Target characteristics

Drugs in development

PLK1 (PLK family)

Target characteristics

Drugs in development

Group: Atypical

Target characteristics

Inhibitors on the market

Inhibitors in development

Dual specificity lipid/protein kinases

PIK3CA (PI3K)

Target characteristics

Inhibitors in development

Future trends

Chapter 4 Non-cancer applications of kinase drugs

Summary

Introduction

Chronic inflammation and kinases

Leading indications

Arthritis

Diabetes

Inflammation

Immunosuppression

Ophthalmology

Psoriasis

Pulmonary diseases

Cardiovascular

Myelodysplastic disorders

GI disorders

Pain

Leading kinase targets

MAPK14

Target characteristics

Inhibitors in development

FRAP1

Target characteristics

Inhibitors on the market

Inhibitors in development

JAK3

Target characteristics

Inhibitors in development

NTRK1

Target characteristics

Inhibitors in development

ROCK1

Target characteristics

Inhibitors on the market

Inhibitors in development

Chapter 5 Leading kinase drug originating companies 238

Summary/Introduction

5.1 Abbott Laboratories

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Ambit Biosciences Corp

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Amgen Inc

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Array BioPharma Inc

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

AstraZeneca plc

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Avila Therapeutics Inc

Company overview

Kinase drug pipeline

Boehringer Ingelheim GmbH

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Bristol-Myers Squibb Co

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Cephalon Inc

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Deciphera Pharmaceuticals LLC

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Eli Lilly Co

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Exelixis Inc

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

GlaxoSmithKline plc

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Hoffmann-La Roche Ltd

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Johnson & Johnson

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Kyowa Hakko Kirin Co Ltd

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Novartis International AG

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Pfizer Inc

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Sanofi-Aventis Group

Company overview

Kinase drug pipeline

Wyeth

Company overview

Kinase-related collaborations (2005 onwards)

Kinase drug pipeline

Chapter 6 Market Analysis: Trends and Forecasts

Summary

Prevalence of targeted diseases

Analyses and Forecasts by Type of Agent

Limus agents/mTOR inhibitors

Overview

Standalone mTOR inhibitors

Drug-eluting stents

Drug-eluting stent market

Sirolimus-eluting stents

Everolimus- and zotarolimus-eluting stents

Sales trends in mTOR inhibitors

Forthcoming mTOR inhibitors

EGFR Family inhibitors

Overview

Trastuzumab

Erlotinib

Cetuximab

Gefitinib

Panitumumab

Lapatinib

Nimotuzumab

Sales trends in EGFR Family inhibitors

Forthcoming EGFR Family Inhibitors

ABL/FLT3 Group Inhibitors

Overview

Imatinib

Dasatinib

Nilotinib

Sales trends in ABL1/FLT3 Family Inhibitors

Forthcoming ABL1/FLT3 Family Inhibitors

VEGFR Family

Overview

Sunitinib

Sorafenib

Sales trends in VEGFR Family inhibitors

Forthcoming VEGFR Family Inhibitors

Other launched agents

Overview

Fasudil

Pirfenidone

Sales trends of other agents

Other forthcoming agents

Company sales and trends

Patenting trends

Appendix 1 Kinase-related targets and their abbreviations

Appendix 2 Other abbreviations and acronyms

Appendix 3 Research Methodology

Index

List of Figures

Figure 1.1: Leading kinase-targeted drug applications

Figure 1.2: Kinase target landscape

Figure 6.3: Kinase originator market shares

List of Tables

Table 1.1: Human Kinase Gene Audit

Table 1.2: Hanks Classification of Protein Kinases (1995)

Table 1.3: Hanks Classification of Protein Kinases (1995) (continued)

Table 1.4: Kinase Agents by Development Stage

Table 1.5: Kinase Drugs by Product Type

Table 1.6: Leading developers of therapeutic kinase-targeted drugs

Table 1.7: Kinase Agonists and Stimulants

Table 3.8: Kinases implicated in human cancer

Table 3.9: Kinases implicated in human cancer (continued)

Table 3.10: Top 20 Kinase Targets in Cancer

Table 3.11: Overview of ABL1-targeted agents in cancer

Table 3.12: Overview of ABL1-targeted agents in cancer (continued 1)

Table 3.13: Overview of ABL1-targeted agents in cancer (continued 2)

Table 3.14: Overview of EGFR-targeted agents in cancer

Table 3.15: Overview of EGFR-targeted agents in cancer (Phase III and above)

Table 3.16: Overview of EGFR-targeted agents in cancer (Phase II)

Table 3.17: Overview of EGFR-targeted agents in cancer (Phase I)

Table 3.18: Overview of EGFR-targeted agents in cancer (Preclinical)

Table 3.19: Overview of ERBB2-targeted agents in cancer (Phase III and above)

Table 3.20: Overview of ERBB2-targeted agents in cancer (Phase II)

Table 3.21: Overview of ERBB2-targeted agents in cancer (Phase I and Preclinical)

Table 3.22: Overview of FLT3-targeted agents in cancer (Launched)

Table 3.23: Overview of FLT3-targeted agents in cancer (Phase II and III)

Table 3.24: Overview of FLT3-targeted agents in cancer (Phase I and II)

Table 3.25: Overview of FLT3-targeted agents in cancer (Preclinical and Phase I)

Table 3.26: Overview of KIT-targeted agents in cancer

Table 3.27: Overview of KIT-targeted agents in cancer (Continued 1)

Table 3.28: Overview of KIT-targeted agents in cancer (Continued 2)

Table 3.29: Overview of KIT-targeted agents in cancer (Continued 3)

Table 3.30: Overview of KIT-targeted agents in cancer (Continued 4)

Table 3.31: Overview of KIT-targeted agents in cancer (Continued 4)

Table 3.32: Overview of PDGFRA-targeted agents in cancer

Table 3.33: Overview of PDGFRA-targeted agents in cancer (Continued 1)

Table 3.34: Overview of PDGFRA-targeted agents in cancer (Continued 2)

Table 3.35: Overview of PDGFRA-targeted agents in cancer (Continued 3)

Table 3.36: Overview of PDGFRB-targeted agents in cancer (Phase II and Phase III)

Table 3.37: Overview of PDGFRB-targeted agents in cancer (Preclinical and Phase I)

Table 3.38: Overview of FLT1-targeted agents in cancer

Table 3.39: Overview of FLT1-targeted agents in cancer (Continued 1)

Table 3.40: Overview of FLT1-targeted agents in cancer (Continued 2)

Table 3.41: Overview of FLT1-targeted agents in cancer (Continued 3)

Table 3.42: Overview of FLT4-targeted agents in cancer

Table 3.43: Overview of FLT4-targeted agents in cancer (Continued 1)

Table 3.44: Overview of FLT4-targeted agents in cancer (Continued 2)

Table 3.45: Overview of KDR-targeted agents in cancer

Table 3.46: Overview of KDR-targeted agents in cancer (Continued 1)

Table 3.47: Overview of KDR-targeted agents in cancer (Continued 2)

Table 3.48: Overview of KDR-targeted agents in cancer (Continued 3)

Table 3.49: Overview of KDR-targeted agents in cancer (Continued 4)

Table 3.50: Overview of KDR-targeted agents in cancer (Continued 5)

Table 3.51: Overview of JAK2-Targeted Agents in Cancer

Table 3.52: Overview of JAK2-Targeted Agents in Cancer (continued)

Table 3.53: Overview of MET-Targeted Agents in Cancer (continued)

Table 3.54: Overview of MET-Targeted Agents in Cancer (continued)

Table 3.55: Overview of AKT1-Targeted Agents in Cancer (continued)

Table 3.56: Overview of AKT1-Targeted Agents in Cancer (continued)

Table 3.57: Overview of CDC2-Targeted Agents in Cancer

Table 3.58: Overview of CDK2-Targeted Agents in Cancer

Table 3.59: Overview of CDK2-Targeted Agents in Cancer (continued)

Table 3.60: Overview of AURKA-Targeted Agents in Cancer

Table 3.61: Overview of AURKA -Targeted Agents in Cancer (continued)

Table 3.62: Overview of AURKB -Targeted Agents in Cancer

Table 3.63: Overview of PLK1 -Targeted Agents in Cancer

Table 3.64: Overview of FRAP1 -Targeted Agents in Cancer

Table 3.65: Overview of FRAP1 -Targeted Agents in Cancer (Continued 1)

Table 3.66: Overview of FRAP1 -Targeted Agents in Cancer (Continued 2)

Table 3.67: Overview of PIK3CA -Targeted Agents in Cancer

Table 3.68: Overview of PIK3CA -Targeted Agents in Cancer (Continued)

Table 4.69: Kinase-Targeted Agents With Anti-Arthritic Applications

Table 4.70: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 1)

Table 4.71: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 2)

Table 4.72: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 3)

Table 4.73: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 4)

Table 4.74: Kinase-Targeted Agents With Anti-Arthritic Applications (continued 5)

Table 4.75: Kinase-Targeted Agents With Diabetes Applications

Table 4.76: Kinase-Targeted Agents With Diabetes Applications (continued 1)

Table 4.77: Kinase-Targeted Agents With Diabetes Applications (continued 2)

Table 4.78: Kinase-Targeted Agents With Inflammatory Applications

Table 4.79: Kinase-Targeted Agents With Inflammatory Applications (Continued 1)

Table 4.80: Kinase-Targeted Agents With Inflammatory Applications (Continued 2)

Table 4.81: Kinase-Targeted Agents With Immunosuppresive Applications

Table 4.82: Kinase-Targeted Agents With Immunosuppresive Applications (continued)

Table 4.83: Kinase-Targeted Agents With Ophthalmological Applications

Table 4.84: Kinase-Targeted Agents With Ophthalmological Applications (continued)

Table 4.85: Kinase-Targeted Agents With Psoriasis Applications (continued)

Table 4.86: Kinase-Targeted Agents With Psoriasis Applications (continued)

Table 4.87: Kinase-Targeted Agents With PulmonaryApplications (Launched)

Table 4.88: Kinase-Targeted Agents With PulmonaryApplications (Phase I-III)

Table 4.89: Kinase-Targeted Agents With PulmonaryApplications (Preclinical)

Table 4.90: Kinase-targeted agents with cardiovascular applications

Table 4.91: Kinase-targeted agents with cardiovascular applications (continued)

Table 4.92: Kinase-targeted agents with myelodysplastic disorder applications

Table 4.93: Kinase-targeted agents with myelodysplastic disorder applications (continued)

Table 4.94: Kinase-targeted agents with myelodysplastic disorder applications (continued 2)

Table 4.95: Kinase-targeted agents with myelodysplastic disorder applications (continued 3)

Table 4.96: Kinase-targeted agents with GI disorder applications

Table 4.97: Kinase-targeted agents with GI disorder applications

Table 5.98: Overview of Abbott's kinase pipeline by status

Table 5.99: Overview of Ambit Biosciences' Kinase Pipeline by Status

Table 5.100: Overview of Amgen's kinase pipeline by status

Table 5.101: Overview of Array BioPharma's kinase pipeline by status

Table 5.102: Overview of AstraZeneca’s kinase pipeline by status

Table 5.103: Overview of Avila Therapeutics' kinase pipeline by status

Table 5.104: Overview of Boehringer Ingelheim's kinase pipeline by status

Table 5.105: Overview of Bristol-Myers Squibb's (BMS) kinase pipeline by status

Table 5.106: Overview of Cephalon's kinase pipeline by status

Table 5.107: Overview of Deciphera Pharmaceuticals' kinase pipeline by status

Table 5.108: Overview of Eli Lilly’s kinase pipeline by status

Table 5.109: Overview of Eli Lilly’s kinase pipeline by status (continued)

Table 5.110: Overview of Exelixis’ kinase pipeline by status

Table 5.111: Overview of Exelixis’ kinase pipeline by status

Table 5.112: Overview of Hoffmann-La Roche's kinase pipeline by status

Table 5.113: Overview of Johnson & Johnson's kinase pipeline by status

Table 5.114: Overview of Kyowa Hakko Kirin's kinase pipeline by status

Table 5.115: Overview of Novartis’ kinase pipeline by status

Table 5.116: Overview of Novartis’ kinase pipeline by status (continued)

Table 5.117: Overview of Pfizer’s kinase pipeline by status

Table 5.118: Overview of Sanofi-Aventis' kinase pipeline by status

Table 5.119: Overview of Wyeth’s kinase pipeline by status

Table 6.120: World Prevalence Of Diseases

Table 6.121: World Pharma Market by Indication (US$m), 2008-2013

Table 6.122: World Pharma Market by Region (US$m), 2008-2013

Table 6.123: Kinase Drug Analysis (in 2007-2008) and Forecasts, 2009-2013 ($USm)

Table 6.124: Kinase Inhibitors by Geography ($USm), 2008 and 2013

Table 6.125: Manufacturer Analysis (2008) and Forecasts (US$m), 2009-2013

Table 6.126: Major Kinase Patent Indications

Table 6.127: Leading Kinase Patent Assignees

Abstract

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