Novel Targets in Drug Discovery
Published By: Drug and Market Development Publishing
November 2006
R294-222
Online Download $4,950.00
Global Site License $24,750.00
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Description
D&MD’s Novel Targets in Drug Discovery report provides an overview of the concept of drug targets, and discusses their place in modern drug discovery. The report looks at the role of technologies such as genomics, proteomics and bioinformatics in target identification, as well as describing the downstream processes such as target validation, lead discovery, lead optimization and clinical development. It also discusses the various types of drug targets using specific examples where appropriate and provides an overview of novel targets currently moving through advanced clinical trials.
In recent years, the process of drug discovery has changed immeasurably. It has gone from a process that was largely disease-focused to one that is target-led. This change has been driven by a number of factors—among them technological advances and economic pressures.
Under the old paradigm, drug discovery began with the identification of a human disease and the development of an animal model of it. Chemical compounds that ameliorated the animal disease were then used as the starting point for the development of a new therapeutic substance. The present approach focuses very much on the identification of potential drug targets, which are typically individual genes or gene products. If the gene underlying a particular disease can be identified, the reasoning goes, then the discovery of chemical compounds or biological agents that modulate the targets, and therefore hopefully treat the disease, can be automated. This approach should be vastly more efficient than dealing with animal models.
However, not everyone agrees that this genetic reductionist approach is valid. While it appears superficially attractive, a number of objections, both theoretical and practical, have been raised. Nevertheless, it has been widely embraced by the pharmaceutical industry. Part of this acceptance is based on the increase pace of life sciences basic research over the past two decades.
This report provides an overview of the concept of drug targets, and discusses their place in modern drug discovery. It looks at the role of technologies such as genomics, proteomics and bioinformatics in target identification, as well as describing the downstream processes such as target validation, lead discovery, lead optimization and clinical development. It also discusses the various types of drug targets using specific examples where appropriate and provides an overview of novel targets currently moving through advanced clinical trials.
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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
- Trion Pharma
- 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
- ã-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
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