:2-Deoxy-D-glucose

{{DISPLAYTITLE:2-Deoxy-D-glucose}}

{{chembox

| Watchedfields = changed

| verifiedrevid = 477213198

| Name = 2-Deoxy-{{sm|d}}-glucose

| Reference =Merck Index, 11th Edition, 2886.

| ImageFile = 2-Deoxy-D-glucose.png

| ImageSize =

| ImageName = 2-Deoxy-D-glucose

| IUPACName = 2-Deoxy-D-arabino-hexopyranose

|SystematicName=(4R,5S,6R)-6-(hydroxymethyl)oxane-2,4,5-triol

| OtherNames = 2-Deoxyglucose
2-Deoxy-{{sm|d}}-mannose
2-Deoxy-{{sm|d}}-arabino-hexose
2-DG

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 4643

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 154-17-6

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 9G2MP84A8W

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 388402

| PubChem = 108223

| EC_number = 205-823-0

| ChEMBL = 2074932

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C6H12O5/c7-2-4-6(10)3(8)1-5(9)11-4/h3-10H,1-2H2/t3-,4-,5?,6+/m1/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = PMMURAAUARKVCB-CERMHHMHSA-N

| SMILES = O[C@H](C(CO)O[C@H](O)C1)[C@H]1O

}}

|Section2={{Chembox Properties

| Formula = C₆H₁₂O₅

| MolarMass = 164.16 g/mol

| Density =

| MeltingPtC = 142 to 144

| MeltingPt_notes =

}}

}}

2-Deoxy-{{sm|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).{{cite journal | last1 = Wick | first1 = AN | last2 = Drury | first2 = DR | last3 = Nakada | first3 = HI | last4 = Wolfe | first4 = JB | year = 1957 | title = Localization of the primary metabolic block produced by 2-deoxyglucose | url = http://www.jbc.org/content/224/2/963.full.pdf | journal = J Biol Chem| volume = 224 | issue = 2| pages = 963–969 | doi = 10.1016/S0021-9258(18)64988-9 | pmid=13405925| doi-access = 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.{{cite journal|last1=Laussel|first1=Clotilde|last2=Léon|first2=Sébastien|date=December 2020|title=Cellular toxicity of the metabolic inhibitor 2-deoxyglucose and associated resistance mechanisms|journal=Biochemical Pharmacology|language=en|volume=182|pages=114213|doi=10.1016/j.bcp.2020.114213|pmid=32890467 |doi-access=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.{{cite journal | last1 = Pelicano | first1 = H | last2 = Martin | first2 = DS | last3 = Xu | first3 = RH | last4 = Huang | first4 = P | year = 2006 | title = Glycolysis inhibition for anticancer treatment | journal = Oncogene | volume = 25 | issue = 34| pages = 4633–4646 | doi=10.1038/sj.onc.1209597 | pmid=16892078| title-link = Glycolysis | doi-access = | s2cid = 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.{{cite journal | doi = 10.1073/pnas.0803090105| pmid = 19004802| pmc = 2584745| title = A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth| journal = Proceedings of the National Academy of Sciences| volume = 105| issue = 46| pages = 17807–17811| year = 2008| last1 = Ralser| first1 = M.| last2 = Wamelink| first2 = M. M.| last3 = Struys| first3 = E. A.| last4 = Joppich| first4 = C.| last5 = Krobitsch| first5 = S.| last6 = Jakobs| first6 = C.| last7 = Lehrach| first7 = H.| bibcode = 2008PNAS..10517807R| doi-access = free}} A synergistic effect between 2-DG and various other agents have been reported in the pursuit of anticancer strategies.{{cite journal |last1=Cheng |first1=Gang |last2=Zielonka |first2=Jacek |last3=Dranka |first3=Brian P. |last4=McAllister |first4=Donna |last5=Mackinnon |first5=A. Craig |last6=Joseph |first6=Joy |last7=Kalyanaraman |first7=Balaraman |date=2012-05-15 |title=Mitochondria-Targeted Drugs Synergize with 2-Deoxyglucose to Trigger Breast Cancer Cell Death |url=https://aacrjournals.org/cancerres/article/72/10/2634/575828/Mitochondria-Targeted-Drugs-Synergize-with-2 |journal=Cancer Research |language=en |volume=72 |issue=10 |pages=2634–2644 |doi=10.1158/0008-5472.CAN-11-3928 |issn=0008-5472 |pmc=3700358 |pmid=22431711}}{{cite journal |last1=Luo |first1=Zhangyi |last2=Xu |first2=Jieni |last3=Sun |first3=Jingjing |last4=Huang |first4=Haozhe |last5=Zhang |first5=Ziqian |last6=Ma |first6=Weina |last7=Wan |first7=Zhuoya |last8=Liu |first8=Yangwuyue |last9=Pardeshi |first9=Apurva |last10=Li |first10=Song |date=March 2020 |title=Co-delivery of 2-Deoxyglucose and a glutamine metabolism inhibitor V9302 via a prodrug micellar formulation for synergistic targeting of metabolism in cancer |journal=Acta Biomaterialia |language=en |volume=105 |pages=239–252 |doi=10.1016/j.actbio.2020.01.019 |pmc=7105957 |pmid=31958597}}{{cite journal |last1=Abebe |first1=Felagot A. |last2=Hopkins |first2=Megan D. |last3=Vodnala |first3=Suraj N. |last4=Sheaff |first4=Robert J. |last5=Lamar |first5=Angus A. |date=2021-07-20 |title=Development of a Rapid In Vitro Screening Assay Using Metabolic Inhibitors to Detect Highly Selective Anticancer Agents |journal=ACS Omega |language=en |volume=6 |issue=28 |pages=18333–18343 |doi=10.1021/acsomega.1c02203 |issn=2470-1343 |pmc=8296616 |pmid=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.{{cite journal|last1=Kurtoglu|first1=M.|last2=Gao|first2=N.|last3=Shang|first3=J.|last4=Maher|first4=J. C.|last5=Lehrman|first5=M. A.|last6=Wangpaichitr|first6=M.|last7=Savaraj|first7=N.|last8=Lane|first8=A. N.|last9=Lampidis|first9=T. J.|date=2007-11-07|title=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|journal=Molecular Cancer Therapeutics|volume=6|issue=11|pages=3049–3058|doi=10.1158/1535-7163.mct-07-0310|pmid=18025288|issn=1535-7163|doi-access=|s2cid=6315384 }}{{cite journal|last1=Xi|first1=Haibin|last2=Kurtoglu|first2=Metin|last3=Liu|first3=Huaping|last4=Wangpaichitr|first4=Medhi|last5=You|first5=Min|last6=Liu|first6=Xiongfei|last7=Savaraj|first7=Niramol|last8=Lampidis|first8=Theodore J.|date=2010-07-01|title=2-Deoxy-d-glucose activates autophagy via endoplasmic reticulum stress rather than ATP depletion|journal=Cancer Chemotherapy and Pharmacology|volume=67|issue=4|pages=899–910|doi=10.1007/s00280-010-1391-0|pmid=20593179|issn=0344-5704|pmc=3093301}}{{cite journal|last1=Defenouillère|first1=Quentin|last2=Verraes|first2=Agathe|last3=Laussel|first3=Clotilde|last4=Friedrich|first4=Anne|last5=Schacherer|first5=Joseph|last6=Léon|first6=Sébastien|date=2019-09-03|title=The induction of HAD-like phosphatases by multiple signaling pathways confers resistance to the metabolic inhibitor 2-deoxyglucose|journal=Science Signaling|volume=12|issue=597|pages=eaaw8000|doi=10.1126/scisignal.aaw8000|pmid=31481524|s2cid=201829818|issn=1945-0877|url=https://hal.archives-ouvertes.fr/hal-03064377/file/Defenouillere%20HAL.pdf}}