創薬における遺伝生化学

Abstract

Introduction

In the drive to streamline the drug discovery process, biotechnology and pharmaceutical companies are harnessing chemical genetics as a tool to overcome the limitations of traditional target-based drug discovery. Although chemical genetics approaches show great potential, their ultimate success can be measured only when drug candidates discovered using these technologies reach the marketplace

Questions Answered in This Spectrum Report

Although chemical genetics was originally developed for basic biological research, industry has enlisted this approach to improve the effectiveness of small-molecule drug discovery and development. What are the potential advantages of chemical genetics for drug discovery, and how will chemical genetics change the current drug discovery model? What technologies enable its use? Several drug candidates derived from chemical genetics programs are now in the early stages of development, some of which are first-in-class agents that may have been difficult to discover by other means. Which companies are utilizing chemical genetics strategies, and what promising agents are in their pipelines? The NIH has launched an initiative to create a comprehensive set of small-molecule compounds that can modulate human genes and their functions, proving that the scientific community believes that chemical genetics has great potential both in biological research and in drug development What are the primary aims of the NIH program? How does the program promise to drive innovation in chemical genetics, and what resources will it offer to commercial and academic researchers?

Scope

• Basics of chemical genetics: development, key aspects, and the central role of diversityoriented synthesis
• Chemical genetics strategies and tools: simultaneous target and lead discovery, diversityoriented synthesis libraries, chemoproteomics strategies, agonists and reversal of loss-offunction, and enabling technologies for chemical genetics
• The NIH Molecular Libraries Roadmap: Molecular Libraries Screening Center Network, PubChem, technology development, and expectations of the MLR initiative Chemical genetics for drug discovery: cellular phenotypic screens, model organisms, and cellular gene expression screens
• Chemoproteomics and chemogenomics methods: approaches involving in vitro affi nity screening of small-molecule compounds against purified proteins
• Outlook for chemical genetics: the impact of chemical genetics on the drug-discovery programs of pharmaceutical and biotechnology companies

Mentioned in This Spectrum Report

Companies

• Abbott Laboratories
• Affymetrix
• Ambit Biosciences
• Amgen
• AstraZeneca
• Avalon Pharmaceuticals
• Biogen Idec
• Bristol-Myers Squibb
• Broad Institute
• Cellzome
• CGI Pharmaceuticals
• CombinatoRx
• Exelixis
• GlaxoSmithKline
• Infi nity Pharmaceuticals
• Johnson & Johnson
• Kosan Biosciences
• Novartis
• Pfi zer
• Sanofi -Aventis
• Schering-Plough
• Serenex
• Synta Pharmaceuticals
• Vertex Pharmaceuticals

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