2-deoxy-2-fluoro-L-fucose

2-deoxy-2-fluoro-L-fucose (also known as 2-fluorofucose or SGN-2FF) is an orally bioavailable small-molecule inhibitor of protein fucosylation. It acts as a fucose analog that is intracellularly metabolized to guanosine diphosphate (GDP)-2-fluorofucose (GDP-2FF). GDP-2FF competitively inhibits fucosyltransferases, such as fucosyltransferase 8 (FUT8), which is responsible for core fucosylation of N-glycans. Additionally, GDP-2FF acts as an allosteric inhibitor of GDP-mannose 4,6-dehydratase (GMDS), thereby depleting the intracellular pool of GDP-fucose. By blocking fucosylation, the drug reduces the levels of fucosylated cell-surface glycoproteins and secreted antibodies, which can inhibit tumor cell growth, decrease metastasis, and enhance antibody-dependent cellular cytotoxicity (ADCC) of therapeutic antibodies. SGN-2FF was developed by Seagen (formerly Seattle Genetics) and evaluated in a Phase 1 clinical trial for advanced solid tumors, both as a monotherapy and in combination with pembrolizumab. However, clinical development was terminated due to safety concerns, specifically the occurrence of thromboembolic events.

Other names

2-FF2-deoxy-2-fluorofucose2-fluorofucose2FF