Kinase Therapeutic Pipelines: An Assessment of Targets and Agents in Development 

By Peter Norman, PhD, MBA

Chapter 1
KINASES
1.1. The Function of Kinases
1.2. The Human Kinome
1.3. Kinase Classification
AGC Family
CAMK Family
CMGC Family
CK1 Family
STE Family
TK Family
TKL Family
Atypical Protein Kinases
1.4. Kinase Structure
1.5. Kinases as Drug Targets

Chapter 2
CURRENT COMMERCIAL SUCCESSES
2.1. Small-Molecule Kinase Inhibitors
Gleevec
Iressa and Tarceva
Nexavar
Sutent
Rapamune and Certican
2.2. Biological Agents

Chapter 3
INDICATIONS FOR THE USE OF KINASE INHIBITORS
3.1. Cancer
3.2. Angiogenic Conditions
3.3. Inflammatory Diseases
3.4. Metabolic Disorders
3.5. Central Nervous System Conditions
3.6. Cardiovascular Disease

Chapter 4
STRATEGIES FOR DEVELOPING KINASE INHIBITORS
4.1. Which Domain to Target?
4.2. Screening Approaches
4.3. Achieving Cellular Activity
4.4. Selectivity Profile
4.5. Pitfalls Encountered
4.6. Intellectual Property Issues
4.7. SWOT Analysis
Strengths
Opportunities
Weaknesses
Threats

Chapter 5
CURRENT PIPELINES
5.1. Overview of Major Company Approaches
Abbott
Amgen
AstraZeneca
Bayer Schering
Boehringer Ingelheim
Bristol-Myers Squibb
Daiichi Sankyo
Eli Lilly
GlaxoSmithKline
Johnson & Johnson
Merck & Co.
Merck Serono
Novartis
Pfizer
Roche
Sanofi-aventis
Schering-Plough
Takeda
Wyeth
5.2. Popular Targets
5.3. Drugs Targeting Protein Kinases that Have Recently Been Approved or Are Awaiting Approval
Lapatinib
Nilotinib
Dasatinib
Sunitinib
Sorafenib
Panitumumab
5.4. Kinase Inhibitors in Phase III
Motesanib
Pazopanib
Aflibercept
Vandetanib
Cediranib
BIBW-2992
Enzastaurin and Ruboxistaurin
Deforolimus
Lestaurtinib
Alvocidib
5.5. Kinase Inhibitors in Phase II
p38 MAP Kinase Inhibitors
      VX-702
      SCIO-469
      Pamapimod
      681323 and 856553
      KC-706
      Other MAP Kinase Inhibitors
      Atypical MAP Kinase Inhibitors
MEK Inhibitors
      PD-325901
      ARRY-142886
PI3K Inhibitors
Akt Inhibitors
      Triciribine
      Perifosine
      INCB-18424
CDK and Chk Inhibitors
      Chk1 Inhibitors
      CDK Inhibitors
      Seliciclib
Abl Inhibitors
      INNO-406
      AT-9283
      MK-0457
      AZD-0530
      Bosutinib
Anti-angiogenic Kinase Inhibitors
      ABT-869
      AEE-788
      BIBF-1120
      Brivanib
      RTA-402
      SU-14813
      SU-6668
      TG-100801
      XL-880
IGFR Inhibitors
      INSM-18
      IMC-A12
      CP-751871
EGFR and ErbB2 Inhibitors
      Neratinib
Flt3 Inhibitors
      Lestaurtinib
      Tandutinib
Inhibitors of Other Kinases
      ABT-263
      Masatinib
      CMI X-11S
      Cethrin
      R-788
      CP-690550
      PHA-739358
      BI-2536
5.6. Kinase Inhibitors in Phase I
Aurora Kinases
Raf Kinase
FGF Inhibitors
Other Kinases
5.7. Outlook

Chapter 6
SPECIALIST COMPANIES
6.1. Structure-Based Approaches
Vertex Pharmaceuticals
6.2. High-Throughput Crystallography
Astex Therapeutics
SGX Pharmaceuticals
6.3. Indication-Based Approaches
AVEO Pharmaceuticals
Cyclacel Pharmaceuticals
Kinex Pharmaceuticals
Oncalis AG
TargeGen
6.4. Domain-Focused Approaches
Ariad Pharmaceuticals
Rigel Pharmaceuticals
Kémia
Piramed Pharma
6.5. Screening-Based Approaches
Ambit Biosciences
Galápagos
Sunesis Pharmaceuticals
Upstate
6.6. Computational Approaches
4SC AG
Amphora Discovery
Aureus Pharma
Emiliem
Locus Pharmaceuticals

Chapter 7
EXPERT INTERVIEWS: A VIRTUAL ROUNDTABLE
Stephen Burley, MD, DPhil, SGX Pharmaceuticals
José Duca, PhD, Schering-Plough Research Institute
David Hayes, PhD, Millipore
Alcide Barberis, PhD, Oncalis AG
Neil Gibson, PhD, OSI Pharmaceuticals
Professor Sir Philip Cohen, FRS, FRSE, Medical Research Council Protein Phosphorylation Unit, University of Dundee
Jeffrey Settleman, PhD, Department of Medicine, Harvard Medical School
References
Company Index with Web Addresses