2-Deoxy-D-glucose
2-Deoxy-Template:Sm-glucose is a glucose molecule 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).[1] 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.[2] 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.[3] 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.[4] A synergistic effect between 2-DG and various other agents have been reported in the pursuit of anticancer strategies.[5][6][7] 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.[8][9][10]
Use in optical imaging
2-DG has been used as a targeted optical imaging agent for fluorescent in vivo imaging.[11][12] 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.Script error: No such module "Unsubst".
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.[13][14] 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".[14][15][16] 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.[15][16]
See also
References
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- ↑ Cheng, Z., Levi, J., Xiong, Z., Gheysens, O., Keren, S., Chen, X., and Gambhir, S., Bioconjugate Chemistry, 17(3), (2006), 662-669
- ↑ What is 2-deoxy-D-glucose (2-DG) and is it effective against Covid?, The Economic Times, 17 May 2021.
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