Chemistry:2-Deoxy-D-glucose

From HandWiki
2-Deoxy-d-glucose[1]
2-Deoxy-D-glucose
Names
IUPAC name
2-Deoxy-D-arabino-hexopyranose
Systematic IUPAC name
(4R,5S,6R)-6-(hydroxymethyl)oxane-2,4,5-triol
Other names
2-Deoxyglucose
2-Deoxy-d-mannose
2-Deoxy-d-arabino-hexose
2-DG
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
EC Number
  • 205-823-0
UNII
Properties
C6H12O5
Molar mass 164.16 g/mol
Melting point 142 to 144 °C (288 to 291 °F; 415 to 417 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

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).[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]

See also

References

  1. ↑ Merck Index, 11th Edition, 2886.
  2. ↑ Wick, AN; Drury, DR; Nakada, HI; Wolfe, JB (1957). "Localization of the primary metabolic block produced by 2-deoxyglucose". J Biol Chem 224 (2): 963–969. doi:10.1016/S0021-9258(18)64988-9. PMID 13405925. http://www.jbc.org/content/224/2/963.full.pdf. 
  3. ↑ Laussel, Clotilde; Léon, Sébastien (December 2020). "Cellular toxicity of the metabolic inhibitor 2-deoxyglucose and associated resistance mechanisms" (in en). Biochemical Pharmacology 182: 114213. doi:10.1016/j.bcp.2020.114213. PMID 32890467. 
  4. ↑ Pelicano, H; Martin, DS; Xu, RH; Huang, P (2006). "Glycolysis inhibition for anticancer treatment". Oncogene 25 (34): 4633–4646. doi:10.1038/sj.onc.1209597. PMID 16892078. 
  5. ↑ Ralser, M.; Wamelink, M. M.; Struys, E. A.; Joppich, C.; Krobitsch, S.; Jakobs, C.; Lehrach, H. (2008). "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. doi:10.1073/pnas.0803090105. PMID 19004802. Bibcode: 2008PNAS..10517807R. 
  6. ↑ 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" (in en). Cancer Research 72 (10): 2634–2644. doi:10.1158/0008-5472.CAN-11-3928. ISSN 0008-5472. PMID 22431711. PMC 3700358. https://aacrjournals.org/cancerres/article/72/10/2634/575828/Mitochondria-Targeted-Drugs-Synergize-with-2. 
  7. ↑ Luo, Zhangyi; Xu, Jieni; Sun, Jingjing; Huang, Haozhe; Zhang, Ziqian; Ma, Weina; Wan, Zhuoya; Liu, Yangwuyue et al. (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" (in en). Acta Biomaterialia 105: 239–252. doi:10.1016/j.actbio.2020.01.019. PMID 31958597. 
  8. ↑ Abebe, 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" (in en). ACS Omega 6 (28): 18333–18343. doi:10.1021/acsomega.1c02203. ISSN 2470-1343. PMID 34308064. 
  9. ↑ Kurtoglu, M.; Gao, N.; Shang, J.; Maher, J. C.; Lehrman, M. A.; Wangpaichitr, M.; Savaraj, N.; Lane, A. N. et al. (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. ISSN 1535-7163. PMID 18025288. 
  10. ↑ 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. doi:10.1007/s00280-010-1391-0. ISSN 0344-5704. PMID 20593179. 
  11. ↑ Defenouillère, 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. doi:10.1126/scisignal.aaw8000. ISSN 1945-0877. PMID 31481524. https://hal.archives-ouvertes.fr/hal-03064377/file/Defenouillere%20HAL.pdf. 
  12. ↑ Kovar, Joy L.; Volcheck, William; Sevick-Muraca, Eva; Simpson, Melanie A.; Olive, D. Michael (2009). "Characterization and performance of a near-infrared 2-deoxyglucose optical imaging agent for mouse cancer models". Analytical Biochemistry 384 (2): 254–262. doi:10.1016/j.ab.2008.09.050. PMID 18938129. PMC 2720560. http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1037&context=biochemfacpub. 
  13. ↑ Cheng, Z., Levi, J., Xiong, Z., Gheysens, O., Keren, S., Chen, X., and Gambhir, S., Bioconjugate Chemistry, 17(3), (2006), 662-669
  14. ↑ What is 2-deoxy-D-glucose (2-DG) and is it effective against Covid?, The Economic Times, 17 May 2021.
  15. ↑ 15.0 15.1 "DCGI approves anti-COVID drug developed by DRDO for emergency use" (in en-IN). 2021-05-08. https://pib.gov.in/PressReleasePage.aspx?PRID=1717007. 
  16. ↑ 16.0 16.1 Borana, Ronak (2021-05-12). "India's Drug Regulator Has Approved DRDO's New COVID Drug on Missing Evidence" (in en-GB). https://science.thewire.in/the-sciences/dcgi-drdo-2-dg-covid-19-treatment-phase-2-3-trials-shoddy-evidence/. 
  17. ↑ 17.0 17.1 Koshy, Jacob (2021-05-11). "Questions remain on DRDO's COVID drug" (in en-IN). The Hindu. ISSN 0971-751X. https://www.thehindu.com/news/national/questions-remain-on-drdos-covid-drug/article34537596.ece. 



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