2-Deoxy-d-glucose is a glucosemolecule which has the 2-hydroxyl group replaced by hydrogen, so that it cannot undergo further glycolysis. As such; it acts to competitively inhibit the production of glucose-6-phosphate from glucose at the phosphoglucoisomerase level (step 2 of glycolysis).[2] 2-Deoxyglucose labeled with tritium or carbon-14 has been a popular ligand for laboratory research in animal models, where distribution is assessed by tissue-slicing followed by autoradiography, sometimes in tandem with either conventional or electron microscopy.
2-DG is up taken by the glucose transporters of the cell.[3] Therefore, cells with higher glucose uptake, for example tumor cells, have also a higher uptake of 2-DG. Since 2-DG hampers cell growth, its use as a tumor therapeutic has been suggested, and in fact, 2-DG is in clinical trials.[4] It is not completely clear how 2-DG inhibits cell growth. The fact that glycolysis is inhibited by 2-DG, seems not to be sufficient to explain why 2-DG treated cells stop growing.[5] A synergistic effect between 2-DG and various other agents have been reported in the pursuit of anticancer strategies.[6][7][8] Because of its structural similarity to mannose, 2DG has the potential to inhibit N-glycosylation in mammalian cells and other systems, and as such induces ER stress and the Unfolded Protein Response (UPR) pathway.[9][10][11]
^Kurtoglu, M.; Gao, N.; Shang, J.; Maher, J. C.; Lehrman, M. A.; Wangpaichitr, M.; Savaraj, N.; Lane, A. N.; Lampidis, T. J. (2007-11-07). "Under normoxia, 2-deoxy-D-glucose elicits cell death in select tumor types not by inhibition of glycolysis but by interfering with N-linked glycosylation". Molecular Cancer Therapeutics. 6 (11): 3049–3058. doi:10.1158/1535-7163.mct-07-0310. ISSN1535-7163. PMID18025288. S2CID6315384.