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Published by: CHI Insight Pharma Reports
Published: Sep. 1, 2003 - 140 Pages Special! Hard copy price reduced to $1500, IOD price reduced to $2150!
Table of Contents
Chapter 1. Introduction: The Importance of Target Validation in the Current Climate
1.1. An Industry in Crisis
Rising R&D Expenditures
Protracted Clinical Trials
Patent Expiry Imminent for Many Blockbusters
A Deficit of New Products
1.2. The Solution
Chapter 2. Scientific Overview: Target Validation and Genomics-Based Drug Discovery Strategies
2.1. What is Target Validation?
2.2. Genomics-Based Drug Discovery Strategies
Technology-Driven Genomics-Based Drug Discovery
Biology-Driven Genomics-Based Drug Discovery
Chemical Genetics
2.3. Can Target Validation Enable the Success of Genomics-Based Drug Discovery?
Chapter 3. Target Identification: The First Stage in Target Evaluation
3.1. Gene Expression Profiling
Limitations of Gene Expression Profiling
3.2. Proteomics Methods
3.3. Structural Proteomics and Mining of Protein Structure Homology Data
3.4. Bioinformatics and Data Mining
3.5. Gene Identification Methods Based on Human Genetics
Chapter 4. Target Characterization
4.1. Elucidation of Biochemical Pathways
4.2. Functional Studies of Specific Genes in Cells
4.3. Molecular Pathology
Chapter 5. Target Validation
5.1. Gene Knockdown Technologies
Antisense RNA
Ribozymes
Interfering RNA
Selected Companies with RNA-Based Knockdown Technologies
5.2. Zinc Finger Proteins and Other Engineered Transcription Factors
5.3. Model Organisms
Use of Yeast and Invertebrate Organisms as Disease Models
Zebrafish as a Model Organism
5.4. Mammalian Disease Models
Complex Animal Models, Target Validation, and Drug Discovery
Gene Knockout Technology
Transgenic Mouse Models
Xenogen’s Biophotonic Imaging
Cellular Genomics’ Analog Sensitive Kinase Allele (ASKA) Mouse Models
5.5. Business Issue: Moving From Technology Companies to Drug Developers
5.6. Use of Forward Genetics in Target Identification and Validation
5.7. Cellular Assays and Chemical Genetics/Genomics in Target Characterization and Validation
Chemical Genetics and Genomics
NeoGenesis’ Automated Ligand Identification System
Rigel’s Combinatorial Biology Approach
Bionaut Sentinel Pathway Reporter System
High-Content Screening
5.8. Protein Inhibition
Chapter 6. Business and Strategic Issues: The Race to Find Valuable Targets
6.1. Expert Commentaries
Alan J. Buckler, Ardais Corporation
Michael Coon, Cell Therapeutics, Inc.
David Dorris, Ambion Inc.
Richard Glynne, Phenomix
Timothy Hoey, Tularik
Leodevico L. Ilag, Xerion Pharmaceuticals AG
Mehran Khodadoust and Thomas Klein, Bionaut Pharma
Kirsten Mundt, ESBATech
James Summerton, Gene Tools
Brian P. Zambrowicz, Lexicon Genetics
Appendix. Selected Company Profiles
Ambion Inc.
Ardais
atugen
Cellomics Inc.
Cellular Genomics Inc.
Cenix BioScience GmbH
Dharmacon
ESBATech AG
Exelixis
GPC Biotech AG
Immusol
Infinity Pharmaceuticals
Lexicon Genetics
NeoGenesis
Nucleonics Inc.
Rigel
Sangamo Biosciences
Sequitur
Xenogen
Zygogen
Glossary
Company Index
Tables and Figures
Table 1: Leading Methods for Elucidation of Signaling Pathways
Table 2: Selected Companies in RNA-Based Knockdown Technologies for Target Validation
Table 3: Selected Companies Using Model Organisms for Target Characterization and Validation
Table 4: Leading Companies in the Area of Large-Scale Mouse Forward Genetics
Figure 1: Large-Scale Genomics-Based Drug Discovery
Figure 2: The Target-Evaluation Continuum
Figure 3: Biology-Driven Genomics-Based Drug Discovery
Figure 4: Model for the Mechanism of RNAi
Figure 5: Breeding Strategy for ENU-Mutagenized Mice
Figure 6: Chemical Genomics Drug Discovery Strategy
Abstract Post-Genomic Target Validation: Next-Generation Approaches and Tools for Optimizing Target Selection evaluates the progress that has occurred over the last couple of years in this field, as well as efforts going forward in the race to develop innovative target validation technologies that will yield the most promising drug leads.
Based on expert commentary and extensive secondary research, Post-Genomic Target Validation profiles the efforts of the leading competitors in this field to sift through the post-genomic data deluge, prioritize targets, and optimize resources to develop the most promising leads. This report comprehensively evaluates the tools and approaches for each step in finding druggable targets— target identification, target characterization, and target validation—and how these tools and approaches differ depending on the type of platform involved. An extensive chapter devoted to target validation examines the limitations of certain technologies, and how to use these tools together for maximum effect. Other critical areas covered in this report include the introduction of RNA interference (RNAi) technology for gene silencing, and the elucidation of biochemical pathways.
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