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Forward & reverse chemical genetics using SPOS-based combinatorial chemistry.

David S Thorpe1

  • 1Department of Discovery Biology, Aventis Combinatorial Technologies Center, Aventis Pharmaceuticals, 1580 E. Hanley Blvd, Tucson, AZ 85737, USA. David.Thorpe@Aventis.com

Combinatorial Chemistry & High Throughput Screening
|December 20, 2003
PubMed
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Chemical genomics utilizes chemical libraries to discover biological effects and identify protein targets. This approach, particularly reverse chemical genetics, is a leading model for modern drug discovery.

Area of Science:

  • Biological Sciences
  • Pharmaceutical Sciences
  • Genetics
  • Genomics

Background:

  • Combinatorial chemistry is a powerful tool applied across biological and pharmaceutical sciences.
  • Chemical genetics, also known as chemical genomics, is an emerging application of this technology.
  • Genetics and genomics are often used interchangeably in this context.

Purpose of the Study:

  • To review the emerging application of chemical genetics/genomics.
  • To describe and illustrate forward and reverse chemical genomics paradigms.
  • To highlight the role of these approaches in biological discovery and drug development.

Main Methods:

  • Forward chemical genomics: Testing chemical libraries in living systems to find compounds with desired effects, followed by protein target identification.

Related Experiment Videos

  • Reverse chemical genomics: Using proteins of interest to probe compound collections, then observing biological responses to compounds that bind these proteins.
  • Utilizing biochemical and molecular biological tools for target identification and inferring protein functions from compound effects.

    • Main Results:

    • Forward chemical genomics provides insights into biological systems and has historically led to drug discovery.
    • Reverse chemical genomics is emerging as a leading model for contemporary drug discovery.
    • Both forward and reverse approaches offer distinct yet valuable strategies for understanding biological processes and identifying therapeutic agents.

    Conclusions:

    • Chemical genomics, encompassing both forward and reverse strategies, offers significant potential for advancing biological understanding and drug discovery.
    • The reverse chemical genetics approach is particularly promising for identifying novel drug candidates.
    • This review illustrates diverse methods and case studies, including those from the author's laboratory, to demonstrate the utility of chemical genomics.