Chemical Genetics in Drug Discovery

Table of Contents

• Executive Summary
• Strategic Considerations
• Stakeholder Implications
• Introduction to Chemical Genetics: The Chemistry-First Strategy
• Basics of Chemical Genetics
• Chemical Genetics Strategies and Tools
• Simultaneous Target and Lead Discovery
• Diversity-Oriented Synthesis Libraries
• Chemoproteomics Strategies
• Agonists and Reversal of Loss-of-Function
• Enabling Technologies for Chemical Genetics
• The NIH Molecular Libraries Roadmap
• Molecular Libraries Screening Center Network
• PubChem
• Technology Development
• Expectations of the MLR Initiative
• Chemical Genetics for Drug Discovery
• Cellular Phenotypic Screens
• CombinatoRx
• CGI Pharmaceuticals
• Synta Pharmaceuticals
• Model Organisms
• Cellular Gene Expression Screens
• Avalon Pharmaceuticals
• GlaxoSmithKline
• The Broad Institute
• Chemoproteomics and Chemogenomics Methods
• Schering-Plough' s Automated Ligand Identification System
• High-Throughput Kinase Screening at Exelixis and Vertex
• Ambit Biosciences' KinomeScan
• Serenex' s Affinity-Based Chemoproteomics Platform
• Cellzome' s Chemical Proteomics Technology
• Outlook for Chemical Genetics

Tables

• 1. Potential Advantages of Chemical Genetics Strategies and Approaches
• 2. Enabling Technologies for Chemical Genetics
• 3. Select Companies Utilizing Cellular or Whole-Organism Phenotypic Screen Technologies for Chemical Genetics
• 4. Companies Utilizing Chemoproteomics or Chemogenomics Technologies
• 5. Select Small-Molecule Agents Discovered Using Chemical Genetics

Figures

• 1. Chemical Genetic Strategy to Discover Compounds That Reverse PTEN Loss-of-Function
• 2. CGI Pharmaceuticals' Analogue Sensitive Kinase Alleles (ASKA) Technology