2-deoxyglucose

Identification

Name
2-deoxyglucose
Accession Number
DB08831
Type
Small Molecule
Groups
Experimental, Investigational
Description

2-deoxyglucose is predominantly used as a diagnostic agent in its radiolabelled form (fluorine-18 is used as the radiolabel). By using positron emission tomography (PET), radiolabelled 2-deoxyglucose can determine glucose metabolism, which is altered in diseases such as cardiovascular disease, tumors, and Alzheimer's disease. Therapeutically, 2-deoxyglucose is an investigational drug that is being studied as an anticancer and antiviral agent. Concerning the former, 2- deoxyglucose was used as an adjunct to chemotherapy and radiotherapy in the treatment of solid tumors (lung, breast, pancreas, head, neck, and gastric tumors). The exact mechanisms of action of 2-deoxyglucose is still being investigated, but it is known that in hypoxic cancer cells, 2-deoxyglucose is a glycolysis inhibitor that prevents ATP production and, ultimately, cell survival. With respect to antiviral therapy, 2-deoxyglucose was shown to be effective against herpes simplex virus by affecting the virus' ability to penetrate cells. As an experimental drug, 2-deoxyglucose was demonstrated to work as an anticonvulsant in temporal lobe epilepsy. In this condition, 2-deoxyglucose represses the expression of certain proteins that are at high levels after a seizure. Although there are several possible therapeutic indications for 2-deoxyglucose, presently there is no approved indication for 2-deoxyglucose as a therapeutic agent.

Structure
Thumb
Synonyms
  • 2-Deoxy-D-arabino-hexose
  • 2-deoxy-D-glucose
  • 2-DG
  • D-arabino-2-desoxyhexose
External IDs
BA 2758 / BA-2758 / NSC-15193
Categories
UNII
9G2MP84A8W
CAS number
154-17-6
Weight
Average: 164.1565
Monoisotopic: 164.068473494
Chemical Formula
C6H12O5
InChI Key
VRYALKFFQXWPIH-PBXRRBTRSA-N
InChI
InChI=1S/C6H12O5/c7-2-1-4(9)6(11)5(10)3-8/h2,4-6,8-11H,1,3H2/t4-,5-,6+/m1/s1
IUPAC Name
(3R,4S,5R)-3,4,5,6-tetrahydroxyhexanal
SMILES
[H]C([H])(C=O)[[email protected]@]([H])(O)[[email protected]]([H])(O)[[email protected]]([H])(O)CO

Pharmacology

Indication

As of July 2013, there is no approved therapeutic indication for 2-deoxyglucose. 2-deoxyglucose may have several potential indications as an adjunct to chemotherapy and radiotherapy in the treatment of solid tumors, as an antiviral treatment in herpes simplex patients, and as an antiepileptic in temporal lobe epilepsy patients.

Structured Indications
Not Available
Pharmacodynamics

Physiologically 2-deoxyglucose is an inhibitor of glycolysis, certain viruses, and seizures.

Mechanism of action

Solid tumors have hypoxic areas with slow growing cells that are resistant to chemotherapy, which attacks rapidly dividing cells. In the hypoxic area of the tumor, the cells rely on anaerobic glycolysis to produce energy in the form of ATP while non-tumor cells can rely on additional pathways such as fatty acid and amino acid metabolism to produce ATP. 2-deoxyglucose is an inhibitor of glycolysis because as a modified glucose molecule (it has a hydrogen at the carbon 2 position instead of a hydroxyl group), it is unable to complete the glycolysis process, and as such will hinder the survival of slow growing cancer cells. Regarding 2-deoxyglucose's antiviral activity, it prevents the glycosylation of specific proteins and lipids as well as prevents proper penetration of the virus into the target cells. In temporal lobe epilepsy, 2-deoxyglucose represses the overactive brain-derived neurotrophic factor (BDNF) promoter and prevents the increased expression of BDNF protein and TrkB receptor (BDNF's receptor) that is observed in epileptic patients.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Korcok J, Dixon SJ, Lo TC, Wilson JX: Differential effects of glucose on dehydroascorbic acid transport and intracellular ascorbate accumulation in astrocytes and skeletal myocytes. Brain Res. 2003 Dec 12;993(1-2):201-7. [PubMed:14642847]
  2. Raez LE, Papadopoulos K, Ricart AD, Chiorean EG, Dipaola RS, Stein MN, Rocha Lima CM, Schlesselman JJ, Tolba K, Langmuir VK, Kroll S, Jung DT, Kurtoglu M, Rosenblatt J, Lampidis TJ: A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Feb;71(2):523-30. doi: 10.1007/s00280-012-2045-1. Epub 2012 Dec 11. [PubMed:23228990]
  3. Garriga-Canut M, Schoenike B, Qazi R, Bergendahl K, Daley TJ, Pfender RM, Morrison JF, Ockuly J, Stafstrom C, Sutula T, Roopra A: 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat Neurosci. 2006 Nov;9(11):1382-7. Epub 2006 Oct 15. [PubMed:17041593]
  4. Spivack JG, Prusoff WH, Tritton TR: A study of the antiviral mechanism of action of 2-deoxy-D-glucose: normally glycosylated proteins are not strictly required for herpes simplex virus attachment but increase viral penetration and infectivity. Virology. 1982 Nov;123(1):123-38. [PubMed:6293188]
External Links
Human Metabolome Database
HMDB62499
KEGG Compound
C00586
PubChem Compound
108223
PubChem Substance
175427111
ChemSpider
97292
ChEBI
15866
ChEMBL
CHEMBL2074932
Wikipedia
2-Deoxy-D-glucose
MSDS
Download (46.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCancer, Breast / Head and Neck Carcinoma / Lung Cancers / Malignant Neoplasm of Pancreas / Malignant Neoplasm of Stomach1
1WithdrawnTreatmentNeoplasms Metastasis / Neoplasms, Intracranial1
1, 2TerminatedTreatmentProstate Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)147°C (296.6°F)From MSDS.
boiling point (°C)DecomposesFrom MSDS.
Predicted Properties
PropertyValueSource
Water Solubility379.0 mg/mLALOGPS
logP-2ALOGPS
logP-2.9ChemAxon
logS0.36ALOGPS
pKa (Strongest Acidic)12.84ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area97.99 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity36.01 m3·mol-1ChemAxon
Polarizability15.47 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.6922
Blood Brain Barrier+0.5304
Caco-2 permeable-0.8684
P-glycoprotein substrateNon-substrate0.6448
P-glycoprotein inhibitor INon-inhibitor0.9436
P-glycoprotein inhibitor IINon-inhibitor0.9738
Renal organic cation transporterNon-inhibitor0.8973
CYP450 2C9 substrateNon-substrate0.8591
CYP450 2D6 substrateNon-substrate0.8744
CYP450 3A4 substrateNon-substrate0.6865
CYP450 1A2 substrateNon-inhibitor0.9823
CYP450 2C9 inhibitorNon-inhibitor0.976
CYP450 2D6 inhibitorNon-inhibitor0.9613
CYP450 2C19 inhibitorNon-inhibitor0.9644
CYP450 3A4 inhibitorNon-inhibitor0.9776
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9888
Ames testNon AMES toxic0.8531
CarcinogenicityNon-carcinogens0.9609
BiodegradationReady biodegradable0.9092
Rat acute toxicity1.0409 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9482
hERG inhibition (predictor II)Non-inhibitor0.9383
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (1 MEOX; 4 TMS)GC-MSsplash10-0q29-1951000000-06cc16a9680628545167
GC-MS Spectrum - GC-MS (1 MEOX; 4 TMS)GC-MSsplash10-0lkc-0951000000-39e56efe41d6473040e4
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0fr5-0920000000-5f7dfef22a1b59cae284
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0ktb-0920000000-6f9638179f688d51022e
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-3900000000-45865b9816a45604d811
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ow-9200000000-7b5a5cbd361ec11efbbf
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0707-9000000000-c9e6d3430eb1073f0d79
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0w29-5900000000-90300437f9ab1170e562
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0k96-9400000000-a11cb0518964ee7a83dd
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-b4574a9d519fced6b332

Taxonomy

Description
This compound belongs to the class of organic compounds known as fatty alcohols. These are aliphatic alcohols consisting of a chain of a least six carbon atoms.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty alcohols
Direct Parent
Fatty alcohols
Alternative Parents
Medium-chain aldehydes / Beta-hydroxy aldehydes / Alpha-hydrogen aldehydes / Secondary alcohols / Polyols / Primary alcohols / Organic oxides / Hydrocarbon derivatives
Substituents
Fatty alcohol / Medium-chain aldehyde / Beta-hydroxy aldehyde / Alpha-hydrogen aldehyde / Secondary alcohol / Polyol / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Primary alcohol
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Xenobiotic transporter activity
Specific Function
Facilitative glucose transporter. This isoform may be responsible for constitutive or basal glucose uptake. Has a very broad substrate specificity; can transport a wide range of aldoses including b...
Gene Name
SLC2A1
Uniprot ID
P11166
Uniprot Name
Solute carrier family 2, facilitated glucose transporter member 1
Molecular Weight
54083.325 Da
References
  1. Korcok J, Dixon SJ, Lo TC, Wilson JX: Differential effects of glucose on dehydroascorbic acid transport and intracellular ascorbate accumulation in astrocytes and skeletal myocytes. Brain Res. 2003 Dec 12;993(1-2):201-7. [PubMed:14642847]

Drug created on February 16, 2013 15:58 / Updated on November 09, 2017 04:41