SGN-2FF

SGN‐2FF (2-fluorofucose) is an orally bioavailable small‐molecule inhibitor of fucosyltransferase that demonstrated encouraging preclinical antitumor activity in mouse models.

SGN‐2FF can fully inhibit the fucosylation of the h1F6 mAb at the lowest screening concentration in CHO cells treated with SGN‐2FF. The functional effect of inhibiting fucosylation of LS174T cells with SGN‐2FF is apparent from its diminished adherence to E-selectin–coated plates.^[2]

LS174T cells are cultured in Eagle MEM with 10% FBS with or without 100 μM SGN‐2FF for 10 d. LS174T xenografts from SGN‐2FF-treated or untreated mice are disaggregated by treatment with collagenase, and loose cells are collected. Cells from either source are washed with PBS solution containing 2% FBS and 0.02% sodium azide and stained with biotinylated LCA, cBR96-Alexa Fluor 488, or SSEAI–Alexa Fluor 488 (1 h on ice). Cells are washed and resuspended in PBS solution/FBS/sodium azide at 4 °C. The lectin-stained cells are treated with FITC-conjugated avidin D (30 min on ice), washed, and then analyzes by flow cytometry.

In mice, SGN‐2FF inhibits fucosylation of endogenously produced antibodies, tumor xenograft membranes, and neutrophil adhesion glycans. SGN‐2FF treatment affords complete protection from tumor engraftment in a syngeneic tumor vaccine model, inhibits neutrophil extravasation, and delays the outgrowth of tumor xenografts in immune-deficient mice. ^[2]