Novel Targets in Drug Discovery

Table of Contents

EXECUTIVE SUMMARY

CHAPTER 1: HISTORICAL PERSPECTIVE

CHAPTER 2: DRUG DISCOVERY IN THE LATE TWENTIETH CENTURY

• The Basis of Inheritance
• The Genetic Code
• Biotechnology
• The Human Genome Project
  • Celera Enters the Race
  • The Major Findings
  • Implications for Drug Discovery
• Functional Genomics
  • Knockouts
  • Antisense
  • RNA Interference
  • Transgenics
  • Limitations of Gene-modified Animal Models
  • DNA Microarrays
• Target Identification
• Target Validation
• Lead Discovery
• Lead Optimization
• Proteomics
• Preclinical Development
• Clinical Development

CHAPTER 3: DRUG DISCOVERY IN THE POST-GENOMIC ERA

• 'Traditional' Drug Discovery
• The Promise of Genomics
  • Genomics and Drug Discovery
  • Unresolved Issues
• Reductionism Criticized
• Target Identification
• Discovery Screens
• How Many Targets?
  • The Druggable Genome
  • Implications for Drug Discovery
• The Importance of Druggability
  • Predicting Druggability
  • Artificial Intelligence

CHAPTER 4: THE NATURE OF DRUG TARGETS

• Nuclear Receptors
• Estrogen Receptors
• Retinoid Receptors
• Vitamin D Receptors
• Glucocorticoid Receptors
• Thyroid Hormone Receptors
• Peroxisome Proliferator-activated Receptors
• Liver X Receptors
• Enzymes
  • Enzyme Inhibitors
• Ion channels
• Receptors
  • G proteins
  • Tyrosine Kinase Receptors
• Hormones and Factors
• Recent Novel Drug Targets

CHAPTER 5: CONCLUSIONS

CHAPTER 6: COMPANY PROFILES

• Aerovance
• Alliance Pharmaceutical
• Cara Therapeutics
• deCODE Genetics
• Elbion
• Genfit
• Nutra Pharma
• Prestwick Pharmaceuticals
• Solbec Pharmaceuticals
• Somaxon

APPENDIX 1: DRUGGABILITY STUDIES

• Other Approaches

APPENDIX 2: RECEPTOR FAMILIES

• Receptor Families
  • Muscarinic Acetylcholine Receptors
  • Adenosine Receptors
  • Adrenergic Receptors
  • Angiotensin Receptors
  • Cannabinoid Receptors
  • Chemokine Receptors
  • Cholecystokinin Receptors
  • Dopamine Receptors
  • Endothelin Receptors
  • γ-aminobutyric Acid (GABA) Receptors
  • Metabotropic Glutamate Receptors
  • Glucagon Receptors
  • Histamine Receptors
  • 5-hydroxytryptamine Receptors
  • Leukotriene Receptors
  • Melanocortin Receptors
  • Melatonin Receptors
  • Neuropeptide Y Receptors
  • P2Y Receptors
  • Opioid Receptors
  • Prostanoid Receptors
  • Somatostatin Receptors
  • Urotensin Receptors
  • VIP and PACAP Receptors

APPENDIX 3: REFERENCES

TABLE OF EXHIBITS

• Exhibit 1.1 Traditional Routes of New Drug Discovery
• Exhibit 1.2 Examples of Ligands Using Various Second Messenger Systems
• Exhibit 1.3 cAMP as a Second Messenger
• Exhibit 2.1 Composition of Nucleic Acids
• Exhibit 2.2 Gene Expression
• Exhibit 2.3 The Central Dogma of Biology
• Exhibit 2.4 What Sequencing the Human Genome Does Not Reveal
• Exhibit 2.5 The Drug Discovery Process
• Exhibit 3.1 Blockbusters whose Success was not Anticipated at the Time of Selection
• Exhibit 3.2 The Biochemical Classes of Therapeutic Drug Targets
• Exhibit 3.3 Number of Potential Drug Targets
• Exhibit 4.1 Typical Concentrations of Ions Inside and Outside the Cell
• Exhibit 4.2 Hormones and Factors used as Drug Targets
• Exhibit 4.3 Distribution of Novel Drug Targets (2004 - 2006)
• Exhibit 4.4 Novel Targets under Development (January 2004 to November 2006)
• Exhibit 4.5 High Potential Drug Development Projects
• Exhibit 4.6 High Potential Development Projects involving Novel Targets
• Exhibit 4.7 Target Involvement of High Potential Projects
• Exhibit 4.8 Large Company Target Involvement
• Exhibit 5.1 Total Market Size Distribution
• Exhibit App2.1 Pharmaceutical Research Involving Dopamine Receptors
• Exhibit App2.2 Classification of 5-HT Receptors