2-Deoxy-D-glucose

{{DISPLAYTITLE:2-Deoxy-D-glucose}} changed 477213198 2-Deoxy-d-glucose Merck Index, 11th Edition, 2886. 2-Deoxy-D-glucose.png 2-Deoxy-D-glucose 2-Deoxy-D-arabino-hexose (3R,4S,5R)-3,4,5,6-Tetrahydroxyhexanal 2-Deoxyglucose2-Deoxy-d-mannose2-Deoxy-d-arabino-hexose2-DG 4643 correct CAS 154-17-6 correct FDA 9G2MP84A8W correct chemspider 388402 108223 205-823-0 2074932 correct chemspider 1S/C6H12O5/c7-2-4-6(10)3(8)1-5(9)11-4/h3-10H,1-2H2/t3-,4-,5?,6+/m1/s1 correct chemspider PMMURAAUARKVCB-CERMHHMHSA-N O[C@H](C(CO)O[C@H](O)C1)[C@H]1O C6H12O5 164.16 g/mol 142 to 144 2-Deoxy-d-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). Wick AN Drury DR Nakada HI Wolfe JB 1957 Localization of the primary metabolic block produced by 2-deoxyglucose http://www.jbc.org/content/224/2/963.full.pdf J Biol Chem 224 2 963–969 10.1016/S0021-9258(18)64988-9 13405925 free 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.Laussel Clotilde Léon Sébastien December 2020 Cellular toxicity of the metabolic inhibitor 2-deoxyglucose and associated resistance mechanisms Biochemical Pharmacology en 182 114213 10.1016/j.bcp.2020.114213 32890467 free 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. Pelicano H Martin DS Xu RH Huang P 2006 Glycolysis inhibition for anticancer treatment Oncogene 25 34 4633–4646 10.1038/sj.onc.1209597 16892078 Glycolysis 22155169 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. 10.1073/pnas.0803090105 19004802 2584745 A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth Proceedings of the National Academy of Sciences 105 46 17807–17811 2008 Ralser M. Wamelink M. M. Struys E. A. Joppich C. Krobitsch S. Jakobs C. Lehrach H. 2008PNAS..10517807R free A synergistic effect between 2-DG and various other agents have been reported in the pursuit of anticancer strategies.Cheng Gang Zielonka Jacek Dranka Brian P. McAllister Donna Mackinnon A. Craig Joseph Joy Kalyanaraman Balaraman 2012-05-15 Mitochondria-Targeted Drugs Synergize with 2-Deoxyglucose to Trigger Breast Cancer Cell Death https://aacrjournals.org/cancerres/article/72/10/2634/575828/Mitochondria-Targeted-Drugs-Synergize-with-2 Cancer Research en 72 10 2634–2644 10.1158/0008-5472.CAN-11-3928 0008-5472 3700358 22431711Luo Zhangyi Xu Jieni Sun Jingjing Huang Haozhe Zhang Ziqian Ma Weina Wan Zhuoya Liu Yangwuyue Pardeshi Apurva Li Song March 2020 Co-delivery of 2-Deoxyglucose and a glutamine metabolism inhibitor V9302 via a prodrug micellar formulation for synergistic targeting of metabolism in cancer Acta Biomaterialia en 105 239–252 10.1016/j.actbio.2020.01.019 7105957 31958597Abebe Felagot A. Hopkins Megan D. Vodnala Suraj N. Sheaff Robert J. Lamar Angus A. 2021-07-20 Development of a Rapid In Vitro Screening Assay Using Metabolic Inhibitors to Detect Highly Selective Anticancer Agents ACS Omega en 6 28 18333–18343 10.1021/acsomega.1c02203 free 2470-1343 8296616 34308064 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.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 10.1158/1535-7163.mct-07-0310 18025288 1535-7163 6315384 Xi Haibin Kurtoglu Metin Liu Huaping Wangpaichitr Medhi You Min Liu Xiongfei Savaraj Niramol Lampidis Theodore J. 2010-07-01 2-Deoxy-d-glucose activates autophagy via endoplasmic reticulum stress rather than ATP depletion Cancer Chemotherapy and Pharmacology 67 4 899–910 10.1007/s00280-010-1391-0 20593179 0344-5704 3093301Defenouillère Quentin Verraes Agathe Laussel Clotilde Friedrich Anne Schacherer Joseph Léon Sébastien 2019-09-03 The induction of HAD-like phosphatases by multiple signaling pathways confers resistance to the metabolic inhibitor 2-deoxyglucose Science Signaling 12 597 eaaw8000 10.1126/scisignal.aaw8000 31481524 201829818 1945-0877 https://hal.archives-ouvertes.fr/hal-03064377/file/Defenouillere%20HAL.pdf Use in optical imaging 2-DG has been used as a targeted optical imaging agent for fluorescent in vivo imaging. 10.1016/j.ab.2008.09.050 18938129 Characterization and performance of a near-infrared 2-deoxyglucose optical imaging agent for mouse cancer models Analytical Biochemistry 384 2 254–262 2009 Kovar Joy L. Volcheck William Sevick-Muraca Eva Simpson Melanie A. Olive D. Michael 2720560 http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1037&context=biochemfacpub Cheng, Z., Levi, J., Xiong, Z., Gheysens, O., Keren, S., Chen, X., and Gambhir, S., Bioconjugate Chemistry, 17(3), (2006), 662-669 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.January 2025 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.What is 2-deoxy-D-glucose (2-DG) and is it effective against Covid?, The Economic Times, 17 May 2021.2021-05-08 DCGI approves anti-COVID drug developed by DRDO for emergency use https://pib.gov.in/PressReleasePage.aspx?PRID=1717007 2021-05-09 Press Information Bureau, Government of India en-IN 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".Borana Ronak 2021-05-12 India's Drug Regulator Has Approved DRDO's New COVID Drug on Missing Evidence https://science.thewire.in/the-sciences/dcgi-drdo-2-dg-covid-19-treatment-phase-2-3-trials-shoddy-evidence/ 2021-05-18 The Wire Science en-GBKoshy Jacob 2021-05-11 Questions remain on DRDO's COVID drug en-IN The Hindu https://www.thehindu.com/news/national/questions-remain-on-drdos-covid-drug/article34537596.ece 2021-05-18 0971-751X 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. See also COVID-19 misinformation Fluorouracil References Category:Deoxy sugars Category:Aldohexoses