Principal Investigator
David Kwan
Concordia University
Project of $934,399 over 3 years
- Supported by CQDM through:
Ministère de l’Économie, de l’Innovation et de l’Énergie du Québec (MEIE) - And by co-funding partners:
– Paraza Pharma inc.
– GlycoSyn
– Mitacs
– Université Concordia
Challenge
Glycosylation is a post-translational modification on most eukaryotic proteins that influences diverse functions such as protein folding, stability, and receptor activation. FUT8-mediated core-fucosylation of N-glycans is essential for mammalian development and this core fucose moiety is critical for the activation of cell-surface receptors like TGFβR, EGFR, and VEGFR. Dysregulation of FUT8 is also a marker and driver of many cancers. Identifying inhibitors of FUT8 would provide new and efficient means of producing therapeutic biologics, namely afucosylated monoclonal antibodies (mAbs), which are more effective at targeting cancer cells in vivo than their fucosylated counterparts.
Solution
Together with Paraza Pharma, the team will implement an automated screening strategy and screen a 50,000-compound library using the fluorescence-based FUT8 activity assay developed by the Kwan lab. While this will be a key step in developing small molecule therapeutics targeting FUT8 in cancer patients, a more immediate application will be as process ingredients for controlling core-fucosylation as a post-translational modification of therapeutic antibodies produced in mammalian cell culture.
Expected Achievements/Impact
Commercialization of FUT8 inhibitors as tools to control glycosylation of biologics production (e.g., cancer targeting therapeutic antibodies) with the field-specific licensing to GlycoSyn will also position us to attract further investment towards development of small molecule therapeutics targeting FUT8 directly in patients.
