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Protein Degradation

  • Overview

    BeyondSpring is at the forefront of research in the protein degradation platform, an alternative approach to cancer treatment in which disease-causing proteins are marked for early degradation. BeyondSpring is one of the few leading companies globally in this field.

    This approach uses a protein called a ubiquitin E3 ligase to target and promote the destruction of disease-causing proteins, such as oncogenes. To trigger degradation, the target protein is labeled with poly-ubiquitin by a specific ubiquitin ligase enzyme. Poly-ubiquitin acts as an indicating tag on cellular proteasome machinery, marking the target protein for destruction.

    BeyondSpring's approach to tagging the target protein is to use a "molecular glue" to bind the ubiquitin ligase to the target protein. We are collaborating with Dr. Ning Zheng, a Howard Hughes Medical Institute Investigator at the University of Washington on a unique "molecular glue" used to selectively tag certain oncogene proteins with E3 ligase, one of the ubiquitin ligase enzymes. Our CEO, Dr. Huang, and Dr. Zheng were the first to discover the crystal structure of the only two classes of E3 ligases. This work forms the structural basis for the selection of small molecules to be studied as a potential "molecular glue". The first target protein is expected to be oncogenes KRAS. KRAS is frequently mutated in pancreas, colon, lung and uterus cancers.

    This novel platform technology has the potential to significantly reduce the amount of oncogene protein in the cell and such disease-causing protein is not targeted by current therapeutic approaches.

  • References

    1Bassermann et al., 2014 Biochimica et Biophysica Acta.
    2Gandhi et al., 2013 British Journal of Haematology.
    3Kronke et al., 2014 Science.
    4Lu et al., 2015 Chemistry & Biology.
    5Metzger et al., 2014 Biochimica et Biophysica Acta.
    6Scheffner et al., 2014 Biochimica et Biophysica Acta.
    7Tan et al., 2007 Nature.
    8Verma et al., 2020 Molecular Cell.

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