Abstract
Recent developments reflect the explosion in the number of kinase inhibitors that have entered clinical development in the past few years:
- By the end of 2006 seven kinase inhibitors had reached the market, three in the period December 2005-December 2006.
- Their collective sales exceeded $4 billion.
- Three more kinase inhibitors have been approved in 2007.
- In addition to ongoing studies of approved kinase inhibitors seeking line extensions, a further 11 are in Phase III studies.
- More than 130 kinase inhibitors are reported to be in either Phase I or Phase II clinical development, with 47 reported to be in Phase II studies.
Protein kinases constitute a large family of proteins that is now firmly established as a major class of drug targets for the pharmaceutical industry. The sequencing of the human genome has led to the identification of 518 protein kinases encoded within it-the human kinome. This constitutes one of the largest and most druggable classes of targets for the pharmaceutical industry, with the number of kinases exceeding the number of G-protein coupled receptors in the human genome.
An essential report for industry professionals working in R&D, portfolio management, and kinase product management, Kinase Inhibitors Pipelines: An Assessment of Targets and Agents in Development reviews the considerable array of drug development efforts directed at kinases and:
- Provides profiles of the activities of the major companies as well as the kinase inhibitors in development, and some of the specialist companies active in the field
- Assesses the potential impact of the more advanced kinase inhibitors, which offer significant market potential
- Discusses some of the technical challenges faced in developing such inhibitors
- Concludes with commentaries from leading experts in the field
With so many inhibitors reported to be in clinical development and many more in preclinical development, kinase inhibitors now make up a significant fraction of most major pharmaceutical companies' pipelines, as well as an area of focus for many biotechnology companies. The increased interest in this class of targets reflects both advances in identifying selective protein kinase inhibitors and a growing perception that these drugs offer a novel, well-tolerated oral therapy in some of the most untreatable cancers.
Although direct kinase inhibitors accounted for only 7% of the value of the oncology market in 2006, their increasing availability and use is likely to be one of the major drivers of growth in this market.
The number of kinase inhibitors in clinical development ensures that during the next 10 years a significant number of such agents will reach the market. The majority of these will be for oncology indications, reflecting the more acute nature of the disease, and thus greater tolerability of potential side effects, and the current emphasis on developing kinase inhibitors for cancer indications.
Table of Contents
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
- p38 MAP Kinase Inhibitors
- 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
