Chapter
1. Background: Targets and Target-Based Drug Discovery and Development
1.1. What Is a Drug Target?
1.2. The Target Validation Problem
Sidebar: Q&A with Dr. Neil W. Gibson, Chief
Scientific Officer of OSI Pharmaceuticals, on Target Validation
1.3. Target Validation and Falling Productivity of Pharmaceutical Research and
Development
1.4. A More Realistic View of Target Validation
1.5. Approaches to Improving the Productivity of Target Evaluation and of Drug
Discovery
Dealing with Multiple Molecular “Causes” of Disease by Hitting More
than One Target
Whole-Pathway Approaches
Biology-Driven Drug Discovery
1.6. Special Issues with Complex Diseases with High Unmet Medical Need
Biomarkers, Targets, and Patient Stratification
Animal Models and Complex Diseases
Chapter 2. Alzheimer’s Disease
2.1. Pathobiology and Mechanistic Studies of Alzheimer’s Disease
Neurotransmitters and Alzheimer's Drugs
The Amyloid Hypothesis
Apolipoprotein E and Alzheimer’s Disease
Mechanistic Studies of Tau and Alpha Synuclein in Alzheimer’s Disease
2.2. Prospects for Biomarkers in Detection of Presymptomatic and Early-Stage
Alzheimer’s Disease and in Monitoring Therapy
2.3. Selected Emerging Targets in Alzheimer’s Disease
Neural Nicotinic Receptors
Beta-Amyloid
Beta-Secretase and Gamma-Secretase
Sidebar: Q&A with Dr. Adrian N. Hobden, President of Myriad Pharmaceuticals,
Inc., on the Challenges of Developing the Novel-Acting Agent Flurizan for Alzheimer’s
Disease
Somatostatin Receptors and Metabolism of Beta-Amyloid
The Tau Pathway
Apolipoprotein E
2.4. Outlook
Chapter 3. Lung Cancer
3.1. Types of Lung Cancer
3.2. Current Diagnosis of Lung Cancer
3.3. Current Therapies for Lung Cancer
3.4. Signaling Pathways and Strategies for Targeted Therapies in Non-Small-Cell
Lung Cancer
3.5. Selected Emerging Targets in Lung Cancer
Epidermal Growth Factor Receptor
K-Ras
B-Raf
Mitogen-Activated Protein Kinase Kinase
Vascular Endothelial Growth Factor Receptor
Aromatose
Hedgehog Signaling Pathway
3.6. Outlook
Chapter 4. Dyslipidemia
4.1. Statins: Their Benefits and Their Limitations
4.2. Mechanistic Issues in Atherogenic Dyslipidemia
Anti-Atherogenic Effects of High-Density Lipoprotein
Metabolic Syndrome, High-Density Lipoprotein, and Triglycerides
4.3. Selected Emerging Targets in Dyslipidemia
Cholesteryl Ester Transfer Protein
Targeting High-Density Lipoprotein with Mimetics
Peroxisome Proliferator-Activated Receptors Alpha and Delta
Liver X Receptor
4.4. Outlook
Chapter 5. Type 2 Diabetes
5.1. Current Therapies
5.2. Difficulties in Drug Discovery in Type 2 Diabetes
5.3. Selected Emerging Targets in Type 2 Diabetes
Dipeptidyl Peptidase-IV
Simultaneous Targeting of PPAR-Alpha and PPAR-Beta
Cannabinoid-1 Receptor
S6 Kinase 1
11 Beta-Hydroxysteroid Dehydrogenase Type 1
Recombinant Adiponectin
Matrix Metalloproteinases
5.4. Outlook
Chapter 6. Chronic Obstructive Pulmonary Disease
6.1. Introduction
Chronic Bronchitis
Emphysema
6.2. Current Treatments
6.3. Animal Models in COPD
6.4. Selected Emerging Targets for COPD
Proteinases (Matrix Metalloproteinases and Neutrophil Elastase)
Phosphodiesterase-4
Oxidant/Antioxidant Balance
Leukotriene B4
CXC Chemokines
Tumor Necrosis Factor-Alpha
6.5. Outlook
Chapter 7. General Conclusions
7.1. Biology-Driven versus Technology-Driven Drug Discovery
7.2. Multitargeted Drugs and Combination Therapies
7.3. Biomarkers, Diagnostics, and Disease Stratification
Chapter 8. Company Profiles
8.1. Alzheimer’s Disease
Axonyx
Elan
Myriad Genetics
Neurochem
Targacept
8.2. Lung Cancer
AstraZeneca
Curis
Genentech
Onyx Pharmaceuticals
OSI Pharmaceuticals
Pfizer
Wyeth
8.3. Dyslipidemia
Avant Immunotherapeutics, Inc.
Exelixis
GlaxoSmithKline
Ligand Pharmaceuticals
Pfizer
8.4. Type 2 Diabetes
Biovitrum
Bristol-Myers Squibb
Merck
Novartis
sanofi-aventis
8.5. Chronic Obstructive Pulmonary Disease
Aeolus Pharmaceuticals
ALTANA Pharma
Arriva
Dompé
Pfizer
References
Glossary
Company Index with Web Sites
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