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Related Experiment Videos

Tethering: fragment-based drug discovery.

Daniel A Erlanson1, James A Wells, Andrew C Braisted

  • 1Sunesis Pharmaceuticals, Inc., 341 Oyster Point Boulevard, South San Francisco, California 94080, USA. erlanson@sunesis.com

Annual Review of Biophysics and Biomolecular Structure
|May 14, 2004
PubMed
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Fragment-based drug discovery using Tethering identifies small molecules that bind protein targets. This method efficiently generates high-affinity drug leads for conditions involving IL-2, TS, PTP-1B, and caspases.

Area of Science:

  • Drug discovery and development
  • Genomics and proteomics
  • Chemical biology

Background:

  • The genomics revolution has identified numerous novel drug targets.
  • Fragment-based approaches are increasingly used for efficient lead molecule identification.
  • Tethering is a fragment-based method for discovering small molecules that bind protein targets.

Purpose of the Study:

  • To review the background and theory of the Tethering method.
  • To discuss the application of Tethering in identifying novel inhibitors.
  • To highlight the use of Tethering for specific protein targets.

Main Methods:

  • Description of the Tethering technique for fragment identification.
  • Elaboration and combination strategies for fragment-derived leads.

Related Experiment Videos

  • Application of Tethering to diverse protein targets.

    • Main Results:

    • Tethering enables the identification of small-molecule fragments with specific protein binding.
    • Fragments can be optimized into high-affinity drug leads.
    • Successful identification of inhibitors for interleukin-2 (IL-2), thymidylate synthase (TS), protein tyrosine phosphatase 1B (PTP-1B), and caspases.

    Conclusions:

    • Tethering is an effective fragment-based approach for drug discovery.
    • The method facilitates the development of novel inhibitors for critical protein targets.
    • This review provides insights into the utility and application of Tethering in medicinal chemistry.