Approaches to Discovering Drugs that Regulate E3 Ubiquitin Ligases

  • J. HuangEmail author
  • L. Tsvetkov
  • K. Qu
  • S. Daniel-Issakani
  • D. G. Payan
Conference paper
Part of the Ernst Schering Foundation Symposium Proceedings book series (SCHERING FOUND, volume 2008/1)


The ubiquitin-proteasome system (UPS) plays an essential role in a wide variety of cell regulatory signaling pathways. The clinical effectiveness of the proteasome inhibitor Velcade in the treatment of several human cancers underscores the importance of the UPS as a novel target area for pharmaceutical intervention. E3 ubiquitin ligases are key enzyme complexes that regulate and determine the ubiquitination of specific substrates, whose abnormal regulation has been implicated in multiple disease phenotypes. Targeting a selective E3 ligase may allow specific manipulation of distinct pathways and eventually lead to a better therapeutic index with reduced nonspecific side effects. Here, we aim to discuss the challenges of interfering with small molecules in this target class, as well as current strategies and progress in E3 ligase drug discovery.


Ring Finger Domain Substrate Ubiquitination Selective Small Molecule Inhibitor Good Therapeutic Index Secondary Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • J. Huang
    • 1
    Email author
  • L. Tsvetkov
    • 1
  • K. Qu
    • 1
  • S. Daniel-Issakani
    • 1
  • D. G. Payan
    • 1
  1. 1.Rigel Pharmaceuticals, Inc.South San FranciscoUSA

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