Today, we’re at the forefront of the protein degradation platform. This innovative and effective approach uses a specific protein (ubiquitin E3 ligase) to target and help destroy disease-causing proteins. We are one of only a few leading global companies in this field.
PROTEIN DEGRADATION IN DETAIL
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. Oncogenic (or disease-causing) proteins can induce cancer by partially mimicking the activity of normal proteins. In tumor cells, oncogenic proteins are often mutated, or expressed, at elevated levels. To trigger protein degradation, the target protein is labeled with poly-ubiquitin using a specific ubiquitin ligase enzyme. Poly-ubiquitin acts as an indicating tag on cellular proteasome machinery, thereby marking a 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” that selectively tags specific oncogene proteins with E3 ligase, one of the ubiquitin ligase enzymes. Dr. Zheng, along with our CEO, Dr. Huang, 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 oncogene protein 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.
- Bassermann et al., 2014 Biochimica et Biophysica Acta.
- Gandhi et al., 2013 British Journal of Haematology.
- Kronke et al., 2014 Science.
- Lu et al., 2015 Chemistry & Biology.
- Metzger et al., 2014 Biochimica et Biophysica Acta.
- Scheffner et al., 2014 Biochimica et Biophysica Acta.
- Tan et al., 2007 Nature.
- Verma et al., 2020 Molecular Cell.