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Kinases: Advanced Strategies and Multiple Targets for Drug Discovery

Published by: Drug and Market Development Publishing

Published: Sep. 1, 2006 - 612 Pages


Table of Contents


Chapter 1: Executive Summary




Chapter 2: Why Target Kinases?

Introduction

Overview of Human Protein Kinases


Classification Schemes


Kinases in Signal Transduction Pathways


MAP Kinase Pathways


MAPK (ERK) Pathway

JNK/SAPK Pathway

p38 MAPK Pathway


PI3K/Akt Signaling

Jak/STAT Signaling


Jak/STAT3 Signaling in Cancer


Insulin Receptor Signaling

NFk-B Pathway


TNF Signaling in Cancer


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

Biopharmaceuticals


Survey of Kinase Inhibitors Under Development


Developing Companies

Indications

Targets

Categories.(origin of material)




Chapter 3: Focus on Small Molecule Kinase Inhibitors

Introduction


Mechanisms of Kinase Inhibition


The Kinase Drug Discovery Process


Improving Target Validation


Use of RNAi and Aptamers


Improving HTS Processes

Improving Structure-based Drug Design

Monitoring Kinase Activity


Primary Screens

Secondary Screens

Cell-based Assays



Identifying Substrates of Novel Kinases


In vitro and In vivo Assays

Use of Peptide Libraries

Use of Protein Microarrays




Chapter 4: Kinase Targets in Cancer

Introduction

Overview of Cancer


Established Therapies

Molecular Targeted Therapies


Kinases in Cancer


Kinase Profiling of Individual Tumors


Inhibiting Multiple Cancer-related Kinases


Multi-Target Kinase


Protein Kinases as Drug Targets

TK Group


Abl Family


Gleevec (imatinib)

Sprycel (dasatinib)

Nilotinib


EGFR Family


Herceptin (trastuzumab)

Erbitux (cetuximab)

Iressa (gefitinib)

Tarceva (erlotinib)

Lapatinib


Eph Family

FGFR Family

VEGFR Family

PDGFR Family

SRC Family

RET Family

TRK Family


TKL Group


RAF Family


AGC Group


AKT Family

PKC Family


CMGC Group


CDK Family

MAPK Family


STE Group

“Other” Group


Aurora Family


Atypical Group

Dual Specificity Lipid/Protein Kinases




Chapter 5: Protein Kinase Targets in Other Diseases

Introduction

Inflammation and Tissue Injury


Background


Current Treatments


Kinase Targets


MAPK14

PRKCA

FRAP1



Diabetes and Insulin Resistance


Background


Current Treatments


Kinase Targets


Kinase Targets of Metformin

GSK3B

PRKCB1

KDR

GCK



Cardiovascular Disease


Background


Percutaneous Coronary Interventions


Kinase Targets


FRAP1

PDGFRA

MAPK14



Other Applications




Chapter 6: Staking Claims to the Human Kinome

Introduction

Overview of Patents

Role of Patents in the Biomedical Industry

Patenting of Genes and Proteins

The Kinase Patent Data Set

Kinase Patent Activities

Forward Citations

Patent Assignees




Chapter 7: Market Considerations and Forecasts

Introduction

The Survey


Preliminary Remarks

Questions and Answers

Conclusions


Kinase Drug R&D: Leading Indications

Kinase Drug R&D: Leading Companies

Kinase Drug R&D: Leading Targets

Kinase Drug Companies, Indications, and Targets

The World Pharmaceutical Market

Kinase Markets


Cancer


Hematologic Cancers

Solid Tumors


Diabetes

Inflammation and Tissue Injury

Cardiovascular Disease

Central Nervous System


Market Analysis and Forecasts


Cancer

Diabetes

Immunology/Inflammation

Cardiology

Central Nervous System

Geographical Markets




Chapter 8: Trends and Opportunities

Kinases: The Big Picture

Actual and Potential Targets of Kinase Drugs

Checking the Commercial Pulse

A Revolution in Cancer Treatment

Drug Resistance: A Pressing Problem

Single Versus Multiple Target Debate




Chapter 9: Company Profiles




Chapter 10: Appendices

Appendix 1: Human Kinase Groups and Family Relationships

Appendix 2: Kinase Companies by Product Portfolio (Summary)

Appendix 3: Kinase Targets by Development Stage

Appendix 4: Associations of Human Protein Kinases with Cancer Amplicons

Appendix 5: Kinase-targeting Anticancer Drugs by Target

Appendix 6: Kinase-Targeting Anticancer Drugs by Company

Appendix 7: Kinase-Targeting Drugs by Indication

Appendix 8: Associations of Human Protein Kinases with Non-Malignant Diseases

Appendix 9: Kinases: Number of Drugs, Targets, and Indications by Company

Appendix 10: Kinase Drugs: Actual, Potential, and Ancillary Targets

Appendix 11: Kinases: Indications by Target

Appendix 12: Kinases: Companies by Target

Appendix 13: Kinases: Indications by Company




Table Of Exhibits

Exhibit 2.1 Hanks Classification of Protein Kinases.(1995)

Exhibit 2.2 Kinase Drugs by Development Stage

Exhibit 2.3 Kinase Indications by Development Stage

Exhibit 2.4 Kinase-targeted Drugs by Origin of Material

Exhibit 6.1 Kinase Patents:.Filing and Publication Dates

Exhibit 6.2 Activity Analysis for US Kinase Patents,.2000-2006

Exhibit 6.3 Top 30 Kinase Patents by Forward Citations.(US Filings 2000-2006)

Exhibit 6.4 Top 40 Kinase Patent Assignees

Exhibit 6.5 Patenting Activities of the Top 15 Kinase Assignees

Exhibit 7.1 List of Respondents’.Organizations

Exhibit 7.2 List of Respondents’.Job Titles

Exhibit 7.3 Job Functions of Survey Respondents

Exhibit 7.4 Target Classes by Commercial Potential

Exhibit 7.5 Kinase Target Subclasses by Commercial Potential

Exhibit 7.6 Kinases:.Multi-target vs Single-target?

Exhibit 7.7 Kinase Inhibitors:.MAbs vs Small Molecules?

Exhibit 7.8 Origins of Kinase Inhibitors

Exhibit 7.9 Indications for Kinase Inhibitors in Development

Exhibit 7.10 Targets for Kinase Inhibitors in Development

Exhibit 7.11 Role of Proteomic Profiling in the Development of Kinase-Targeted Drugs

Exhibit 7.12 Indications for Kinase Inhibitors Currently on the Market

Exhibit 7.13 Targets for Kinase Inhibitors Currently on the Market

Exhibit 7.14 Most Promising Market Segments for Kinase Inhibitors

Exhibit 7.15 Target Acquisition Strategies

Exhibit 7.16 Target Development Strategies

Exhibit 7.17 Kinase Drug Indications by Development Stage

Exhibit 7.18 Company Product Portfolios by Development Stage

Exhibit 7.19 Kinase Targets by Development Stage

Exhibit 7.20 World Pharma Market by Region in 2005 and 2010

Exhibit 7.21 World Pharma Market by Indication in 2005 and 2010

Exhibit 7.22 Kinase Market Forecasts by Indication,.2005-2010

Exhibit 7.23 Kinase Market Forecasts by Region,.2005-2010

Abstract

The kinase-targeted drug market is forecast to reach $58.6 billion in 2010.

D&MD's Kinases: Advanced Strategies for Drug Discovery market analysis report comprehensively reviews protein kinases and assesses their importance as drug targets. Approaches to kinase drug discovery are evolving. Small molecule inhibitors now encompass rationally-designed single-target inhibitors and multi-target inhibitors developed with the aid of new screening and profiling assays. Innovative biopharmaceuticals are making inroads into the market. The range of indications for kinase-targeted drugs is expanding.

During the last five years, eight anticancer kinase inhibitors received FDA approval, including multi-kinase inhibitors, the first of which was approved by the FDA in December 2005. The launched drugs are discussed in this report, as are similar agents that are following in their track. At the same time, recent discoveries of activating and resistance kinase mutations have been driving the development of molecularly targeted anticancer therapies and we review progress in this area. An on-line survey conducted specially for this report shows that kinases (alongside GPCRs), are currently regarded as commercially the most promising targets available to the drug industry. The facts and analysis provided by this report help companies prepare themselves to exploit these targets.

Buy this report and receive:
  • Results from a survey of more than 800 kinase drugs and their targets to give the reader an appreciation of the kinase drug landscape
  • Current market size and forecasts to 2010 to assist the reader with formulating business plans in the kinase drug area
  • Analysis on the leading indications for kinase drugs and highlights in areas of unmet needs to enable the reader to formulate a strategy for business development
  • Profiles of kinase-related patenting at the US PTO to help the reader understand the area's evolving IP landscape, identify trends, improve strategic approach and discover potential collaborative partners
  • Comprehensive analysis of kinase drug targets through a gene family-based approach to allow the reader to assess the drug development potential of kinases belonging to particular families
Receive answers to crucial questions in this area such as:
  • Which kinase targets are being pursued by drug developers?
  • Which kinase targets have attracted the greatest amount of interest from drug developers?
  • What is the nature of commercial activity surrounding each major kinase target?
  • Which are the most important therapeutic indications for kinase drugs?
  • What are the areas of unmet need that new kinase drugs could address?
  • Which companies are the most prolific developers of kinase drugs and what drugs are in their portfolios?
  • Who are the most prolific assignees and which are the most frequently cited kinase patents?
Recent approvals of several first-in-class kinase inhibitors have resulted in increased recognition of kinases as an important class of drug targets. The kinase market is still at an early stage, but many trends are already evident and these are analyzed in this report. Already 145 kinase-related genes are being targeted in kinase drug development, which nonetheless leaves a large number (estimated 627) of potential targets unexplored. This report guides readers in assessing or reassesing their strategies with respect to this target class.

In order to comprehensively assess recent progress and prospects in the kinase field, several surveys were carried out exclusively for this report, involving searches of the Pharmaprojects database and the U.S. Patent and Trademark Office database, and questioning of respondents from the pharmaceutical industry. The information from the various surveys was utilized in the analysis of individual kinase targets and families to which they belong.

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