Author: 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
INDICATIONS
2.1. Introduction
2.2. Cancer
2.3. Angiogenic Conditions
2.4. Inflammatory Diseases
2.5. Metabolic Disorders
2.6. CNS Conditions
2.7. Cardiovascular Disease
CHAPTER 3
R&D CONSIDERATIONS
3.1. Introduction
3.2. Kinase Selectivity
Profiling
Selectivity Profiles of Selected Inhibitors
How Selective?
3.3. Structural Features
X-Ray Structures and Multiple Conformations
3.4. Kinase Mutations
Bcr-Abl
Pharmacogenomics
3.5. Intellectual Property Issues
CHAPTER 4
CURRENT COMMERCIAL SUCCESSES
4.1. Introduction
4.2. Small Molecules
Overview
Abl Inhibitors
Gleevec (imatinib)
Tasigna (nilotinib) and Sprycel (dasatinib)
EGF Family Inhibitors
Tarceva (erlotinib) and Iressa (gefitinib)
Tykerb (lapatinib)
Multi-Kinase Inhibitors
Nexavar (sorafenib)
Sutent (sunitinib)
Palladia (toceranib) and Masivet (mastinib)
mTOR Inhibitors
Rapamune (sirolimus)
Torisel (temsirolimus), Afinitor/Certican (everolimus), Endeavor (zotarolimus)
Rho Inhibitor
Eril (fasudil)
4.3. Biological Agents
CHAPTER 5
CURRENT KINASE INHIBITOR PIPELINES
5.1. Introduction
5.2. Overview
5.3. Kinase Inhibitors in Phase III
Enzastaurin and Ruboxistaurin
Midostaurin
Pan-VEGFR Inhibitors
Votrient (pazopanib)
Cediranib
Motesanib
Axitinib
Aflibercept
Vandetanib
BIBW-2992
Neratinib
Pertuzumab
FGFR Inhibitors
BIBF-1120
Brivanib
Alvocidib
Bosutinib
Lestaurtinib
Ridaforolimus
Masitinib
BMS-907351
CP-690550
INCB-18424
5.4. Kinase Inhibitors in Phase II Development
5.5. Kinase Inhibitors in Phase I Development
5.6. Growth Factor Receptor Kinases
ErbB Family Kinases
ErbB2 and ErbB3
ErbB2 and EGFR
Pan-ErbB
Antibodies
FGF
IGF
VEGF
Multi-Kinase Inhibitors
Flt3
5.7. Popular Kinase Cascades
PI3K, Akt, mTOR, S6K
Perifosine
Triciribine
Archexin
Ras, Raf, MEK, ERK
Roche
Ardea Biosciences and Bayer
Array and AstraZeneca
JAK Family
5.8. Cell Cycle Inhibitors
Cyclic-Dependent Kinase (CDK)
Checkpoint Kinase (Chk)
Polo-Like Kinase (PLK)
BI-2536 and BI-6727
5.9. Popular Kinase Targets
Abl
p38
GSK-3
Protein Kinase C
Aurora
Broad Spectrum
Pan-Aurora
Aurora 1
Aurora 2
c-Met
Rho
JNK
Src Family
Kinases in Inflammatory Diseases
5.10. Other Kinases
Serine/Threonine Kinases
Tyrosine Kinases
Tyrosine-Like, CAMK, and Atypical Kinases
5.11. Outlook
CHAPTER 6
CORPORATE ACTIVITIES
6.1. Introduction
6.2. Major Companies
Abbott
Amgen
Astellas
AstraZeneca
Bayer
Boehringer Ingelheim
Bristol-Myers Squibb
Daiichi Sankyo
Eisai
Eli Lilly
GlaxoSmithKline
Johnson & Johnson
Merck & Co.
Merck Serono
Novartis
Pfizer
Roche
sanofi-aventis
Takeda
6.3. Specialist Companies
ACT Biotech
Advenchen
Array BioPharma
Avila Therapeutics
Calistoga Pharmaceuticals
Cellzome
Cyclacel Pharmaceuticals
Cylene Pharmaceuticals
Deciphera Pharmaceuticals
Emiliem
Exelixis
Intellikine
Kai Pharmaceuticals
Nerviano Medical Sciences
Oncalis
OSI Pharmaceuticals
Rigel Pharmaceuticals
S*Bio
Semafore Pharmaceuticals
SuperGen
TargeGen
Vertex Pharmaceuticals
6.4. Service Companies
Ambit Biosciences
Galapágos
Invitrogen
KINAXO Biotechnologies
ProQinase
SignalChem
Upstate (Millipore)
CHAPTER 7
MARKET OUTLOOK
7.1. Introduction
7.2. Near-Term Developments
7.3. Longer-Term Outlook
CHAPTER 8
EXPERT INTERVIEWS
REFERENCES
COMPANY INDEX WITH WEB ADDRESSES