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Chemical Genetics in Drug Discovery

Published by: Decision Resources

Published: Nov. 30, 2006 - 24 Pages

Price reduced due to age.

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

Abstract

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 affinity 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.

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