Kinases: Advanced Strategies and Multiple Targets for Drug Discovery

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