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]
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]
[1] Khanh T Do, et al. Oncologist. 2021 Nov;26(11):925-e1918. [2] Nicole M Okeley, et al. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5404-9.