Glucose metabolism; glycolysis; hexokinase; HSV-1; Antimetabolites; Antiviral Agents

In MCF-7 cells, 2-Deoxy-D-glucose (2-DG), 4, 8, or 16 mM, dramatically decreased ATP levels in a dose- and time-dependent manner that was comparable to the effect of 2-DG on cell growth. exposure to 4, 8 or 16 mM 2-Deoxy-D-glucose 1, 3 or for 5 days in a way that depends on the dose and the amount of time [1]. When 2-DG is administered, pentose phosphate pathway (PPP) responders are upregulated, and 6-phosphate endpoint dehydrogenase produces more NADPH. The 2-DG reduced form of glutathione is elevated in NB4 cells due to an increase in NADPH and an upregulation of glutathione synthetase expression [3].

2-Deoxy-D-glucose (0.03%, w/w) postponed the possible beginning of breast cancer and led to a statistically significant 7% reduction in final body weight [1]. 2. During extraction, 2-Deoxy-D-glucose (3 mmol/kg, iv) is lowered in a dose-dependent manner [2].
Note: Despite the numerous preclinical and clinical studies, the use of 2-DG in cancer and viral treatment has been limited. Its rapid metabolism and short half-life (according to Hansen et al., after treatment with infusion of 50 mg/kg2-DG, its plasma half-life was only 48 min), make 2-DG a relatively poor drug candidate. Moreover, 2-DG must be given at relatively high concentrations (≥5 mmol/L) to compete with blood glucose. According to Stein et al., the dose of 45 mg/kg received orally on days 1–14 was defined as safe because patients did not experience any dose-limiting toxicities. Notably, at the dose of 60 mg/kg, two patients experienced dose-limiting toxicity of grade 3–asymptomatic QTc prolongation. According to former studies published by Burckhardt et al. and Stalder et al., among patients exposed to 2-DG, non-specific T wave flattening and QT prolongation, without any event of severe arrhythmia, developed.[4]

ATP assay. The effect of 2-DG on ATP level in the cells was determined using an ENLITEN ATP assay kit (Promega Corporation, Kadison, WI), the bioluminescence was detected using a TD 20/20 luminometer (Turner Biosystem, Sunnyvale, CA), and the amount of ATP per well was standardized by the cell number estimated by crystal violet method described above.[1]

Using MCF-7 human breast cancer cells to investigate the signaling pathways perturbed by disruption of glucose metabolism, 2-DG reduced cell growth and intracellular ATP in a dose- and time-dependent manner (P < 0.01). Treatment with 2-DG increased levels of phosphorylated AMP-activated protein kinase and Sirt-1 and reduced phosphorylated Akt (P < 0.05). These studies support the hypothesis that DER inhibits carcinogenesis, in part, by limiting glucose availability and that energy metabolism is a target for the development of ERMA for chemoprevention.[1]

For the carcinogenesis study, ninety 21-day-old female Sprague-Dawley rats were injected i.p. with 50 mg of 1-methyl-1-nitrosourea per kilogram of body weight. Following injection, animals were ad libitum fed AIN-93G diet containing 0.00%, 0.02%, or 0.03% (w/w) 2-DG for 5 weeks. 2-DG decreased the incidence and multiplicity of mammary carcinomas and prolonged cancer latency (P < 0.05). The 0.02% dose of 2-DG had no effect on circulating levels of glucose, insulin, insulin-like growth factor-I, IGF binding protein-3, leptin, or body weight gain. [1]

Absorption, Distribution and Excretion
WHEN THE RENAL EXCRETION OF 2-DEOXYGLUCOSE WAS STUDIED IN DOGS AND RATS BY CONVENTIONAL CLEARANCE AND STOP-FLOW TECHNIQUES, IT WAS REABSORBED BY THE RENAL TUBULES AT AN AVG OF 68-89% OF THE FILTERED LOADS AND THE REABSORPTION SITE WAS IN THE PROXIMAL TUBULES.

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Metabolism / Metabolites
2-DEOXY-D-GLUCOSE WAS CONVERTED TO THE 6-PHOSPHATE IN MOUSE TESTIS AND LIVER AFTER IP INJECTION OF 50 MG/KG BODY WT DAILY FOR 7 DAYS.

Interactions
2-DEOXYGLUCOSE INJECTED INTRAPERITONEALLY IN RATS IN LARGE DOSES CAUSED CHANGES IN THE ELECTRORETINOGRAM CONSISTING OF A DECR IN BOTH ALPHA- AND BETA-WAVES. THE EFFECT WAS ANTAGONIZED BY D-GLUCOSE. Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 353

SIMULTANEOUS ADMIN OF GLUCOSE @ DOSE EXCEEDING ITS MAX TUBULAR TRANSPORT CAPACITY INHIBITED TUBULAR REABSORPTION OF 2-DEOXYGLUCOSE. THUS, THE PROCESS OF TUBULAR REABSORPTION IS PROBABLY THE SAME AS THAT FOR GLUCOSE. WOOSLEY RL ET AL; RENAL TUBULAR TRANSPORT OF 2-DEOXY-D-GLUCOSE IN DOGS AND RATS; J PHARMACOL EXP THER 173(1) 13 (1970)

IN ANESTROUS SHEEP, 2-DEOXYGLUCOSE INFUSION INHIBITED LH RELEASE INDUCED BY ESTRADIOL BUT NOT BY LH-RH. CRUMP AD ET AL; ESTRADIOL-INDUCED LUTEINIZING HORMONE (LH) RELEASE IS INHIBITED BY 2-DEOXYGLUCOSE INFUSION IN SHEEP; J PHYSIOL (LONDON) 330: 93P (1982)

2-DEOXY-D-GLUCOSE INHIBITED REPAIR OF POTENTIALLY LETHAL DAMAGE INDUCED BY X-RAYS IN MOUSE EHRLICH ASCITES TUMOR CELLS.

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Non-Human Toxicity Excerpts
2-DEOXYGLUCOSE INJECTED INTRAPERITONEALLY IN RATS IN LARGE DOSES CAUSED CHANGES IN THE ELECTRORETINOGRAM CONSISTING OF A DECR IN BOTH ALPHA- AND BETA-WAVES. Grant, W. M. Toxicology of the Eye. 2nd ed. Springfield, Illinois: Charles C. Thomas, 1974., p. 353
...120 MG/DAY /GIVEN TO RAT/ FROM THE 9TH THROUGH THE 20TH GESTATIONAL DAY... RESORPTIONS WERE 69% AND THE SURVIVING FETUSES WERE ALL MALFORMED. ANOPHTHALMIA, CLEFT LIP AND PALATE AND LESIONS OF THE EXTREMITIES WERE OBSERVED. ...GAVE 1 G/KG ON DAYS 8, 9, 10 OR 11 & FOUND NO MALFORMATIONS IN SURVIVING RAT FETUSES.

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Interactions
2-DEOXYGLUCOSE INJECTED INTRAPERITONEALLY IN RATS IN LARGE DOSES CAUSED CHANGES IN THE ELECTRORETINOGRAM CONSISTING OF A DECR IN BOTH ALPHA- AND BETA-WAVES. THE EFFECT WAS ANTAGONIZED BY D-GLUCOSE.
SIMULTANEOUS ADMIN OF GLUCOSE @ DOSE EXCEEDING ITS MAX TUBULAR TRANSPORT CAPACITY INHIBITED TUBULAR REABSORPTION OF 2-DEOXYGLUCOSE. THUS, THE PROCESS OF TUBULAR REABSORPTION IS PROBABLY THE SAME AS THAT FOR GLUCOSE.
IN ANESTROUS SHEEP, 2-DEOXYGLUCOSE INFUSION INHIBITED LH RELEASE INDUCED BY ESTRADIOL BUT NOT BY LH-RH.
2-DEOXY-D-GLUCOSE INHIBITED REPAIR OF POTENTIALLY LETHAL DAMAGE INDUCED BY X-RAYS IN MOUSE EHRLICH ASCITES TUMOR CELLS.
For more Interactions (Complete) data for 2-DEOXY-D-GLUCOSE (6 total), please visit the HSDB record page.

[1]. Zhu Z, et al. 2-Deoxyglucose as an energy restriction mimetic agent: effects on mammary carcinogenesis and on mammary tumor cell growth in vitro. Cancer Res. 2005 Aug 1;65(15):7023-30.
[2]. Ueyama A, et al. Nonradioisotope assay of glucose uptake activity in rat skeletal muscle using enzymatic measurement of 2-deoxyglucose 6-phosphate in vitro and in vivo. Biol Signals Recept. 2000 Sep-Oct;9(5):267-74.
[3]. Miwa H, et al. Leukemia cells demonstrate a different metabolic perturbation provoked by 2-deoxyglucose. Oncol Rep. 2013 May;29(5):2053-7
[4]. Int J Mol Sci. 2020 Jan; 21(1): 234.

2-deoxy-D-glucose has been reported in Streptomyces nigra with data available.
2-Deoxy-D-glucose is a non-metabolizable glucose analog in which the hydroxyl group at position 2 of glucose is replaced by hydrogen, with potential glycolysis inhibiting and antineoplastic activities. Although the exact mechanism of action has yet to be fully elucidated, upon administration of 2-deoxy-D-glucose (2-DG), this agent competes with glucose for uptake by proliferating cells, such as tumor cells. 2-DG inhibits the first step of glycolysis and therefore prevents cellular energy production, which may result in decreased tumor cell proliferation.
2-deoxy-D-glucose is a metabolite found in or produced by Saccharomyces cerevisiae.
2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.

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Therapeutic Uses
Antimetabolites; Antiviral Agents
MEDICATION (VET): TOPICAL TREATMENT OF HERPES GENITALIS IN FEMALE GUINEA PIGS WITH 2-DEOXY-D-GLUCOSE IN EITHER AGAROSE GELS OR MICONAZOLE NITRATE OINTMENT FAILED TO PREVENT DEVELOPMENT OF GENITAL LESIONS OR TO REDUCE THE MEAN TITERS OF RECOVERABLE VIRUS IN VAGINAL SWABS FROM INFECTED ANIMALS.

C6H12O5

164.1565

164.068

C, 43.90; H, 7.37; O, 48.73

154-17-6

2-Deoxy-D-glucose-d;188004-07-1;2-Deoxy-D-glucose-13C;201612-55-7;2-Deoxy-D-glucose-13C-1;119897-50-6

108223

White to off-white solid powder

1.4±0.1 g/cm3

456.7±45.0 °C at 760 mmHg

146-147ºC

244.1±25.2 °C

0.0±2.5 mmHg at 25°C

1.534

Endogenous metabolite

-3.07

4

5

5

11

116

3

O([H])[C@]([H])([C@@]([H])(C([H])([H])O[H])O[H])[C@@]([H])(C([H])([H])C([H])=O)O[H]

VRYALKFFQXWPIH-PBXRRBTRSA-N

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

2-Deoxy-D-arabinohexose

2-deoxy-D-glucose; Deoxyglucose; 154-17-6; 2-Deoxy-D-arabino-hexose; 2-Desoxy-D-glucose; 2-DG; (3R,4S,5R)-3,4,5,6-tetrahydroxyhexanal; 2-Deoxy-D-mannose;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 24 mg/mL (~146.20 mM)

Solubility in Formulation 1: 130 mg/mL (791.91 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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Solubility in Formulation 2: ~130 mg/mL (~792 mM) in PBS

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 (Please use freshly prepared in vivo formulations for optimal results.)