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]
Use in optical imaging
2-DG has been used as a targeted optical imaging agent for fluorescent in vivo imaging.[12][13] In clinical medical imaging (
PET scanning),
fluorodeoxyglucose is used, where one of the 2-hydrogens of 2-deoxy-D-glucose is replaced with the positron-emitting isotope
fluorine-18, which emits paired
gamma rays, allowing distribution of the tracer to be imaged by external gamma camera(s). This is increasingly done in tandem with a
CT function which is part of the same PET/CT machine, to allow better localization of small-volume tissue glucose-uptake differences.
Indian adoption for COVID-19 treatment
On May 8, 2021, the
Drugs Controller General of India approved an oral formulation of 2-deoxy-D-glucose for emergency use as adjunct therapy in moderate to severe coronavirus patients.[14][15]
The drug was developed by the
DRDO along with
Dr. Reddy's Laboratories, who jointly claimed via a press release, that the drug "helps in faster recovery of hospitalised patients and reduces supplemental oxygen dependence".[15][16][17]The Wire as well as
The Hindu noted that the approval was based on poor evidence; no journal publication (or
preprint) concerning efficacy and safety are yet available.[16][17]
^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.