2-Deoxyglucose Studies

2-Deoxyglucose is the most commonly used glycolytic inhibitor in plate-based experiments, and in some contexts its use can be difficult to interpret.

　

International Journal of Biochemistry
Volume 18, Issue 4, 1986, Pages 311-318
International Journal of Biochemistry
2-deoxy-d-glucose metabolism in individual tissues of the rat in vivo
.JenkinsS.M.FurlerE.W.Kraegen

Abstract
1.
1. The nature of and rates of loss of products of systemic radiolabelied 2-deoxy-d-glucose in rat tissues in vivo were investigated to validate the use of this tracer to measure rates of metabolism of circulating glucose by tissues in vivo.

2.
2. Apparent first order rate constants for loss of products ranged from 8.0 ± 0.10(SD) × l0−3min−1 (liver) to 2.2 ± 0.8 × l0−3min−1 (skeletal muscle).

3.
3. 2-deoxyglucose 6-phosphate was the major product found in all tissues examined except liver; all tissues contained other minor products.

4.
4. Products were effectively trapped by rat tissues in vivo allowing the use of this tracer for the measurement of rates of circulating glucose utilisation by tissues in vivo.

2-deoxy-d-glucose metabolism in individual tissues of the rat in vivo - ScienceDirect
https://www.sciencedirect.com/science/article/abs/pii/0020711X86900364

　

Targeting Altered Metabolism—Emerging Cancer Therapeutic Strategies
Minsuh Seo, ... Yong-Hwan Lee, in Cancer Drug Design and Discovery (Second Edition), 2014

2-Deoxyglucose
2-Deoxyglucose (2-DG), a derivative of glucose, is able to be phosphorylated by hexokinase, resulting in the formation of 2-deoxyglucose-phosphate (2-DG-P) [89]. The product of this reaction is trapped within the cell and cannot be used by subsequent steps of glycolysis, resulting in the accumulation of 2-DG-P and causing product inhibition of HK2 [90]. In vitro studies on 2-deoxyglucose have demonstrated HK2 inhibition as well as subsequent ATP depletion; however, in vivo studies using xerographs have been disappointing, showing that 2-deoxyglucose as a single agent does not inhibit tumor growth. However, new evidence suggests that this compound does offer some benefit when used in combination with other drugs that target tumor metabolism.

2-Deoxy-D-Glucose - an overview | ScienceDirect Topics
https://www.sciencedirect.com/topics/neuroscience/2-deoxy-d-glucose

　

Dual metabolic reprogramming by ONC201/TIC10 and 2-Deoxyglucose induces energy depletion and synergistic anti-cancer activity in glioblastoma | British Journal of Cancer
https://www.nature.com/articles/s41416-020-0759-0

　

　

　

CNS Pharma up 22% premarket on 2-DG action against coronavirus
Apr. 13, 2020 9:05 AM ET|About: CNS Pharmaceuticals, Inc. (CNSP)|By: Douglas W. House, SA News Editor
Thinly traded nano cap CNS Pharmaceuticals (NASDAQ:CNSP) jumps 22% premarket on average volume in reaction to its announcement that research performed at the University of Frankfurt showed the 2-deoxy-D-glucose (2-DG) totally blocked replication of SARS-CoV-2, the virus causing COVID-19, in a cell culture model.

The findings were submitted to NatureResearch about a month ago.

The company is collaborating with WPD Pharmaceuticals (OTCPK:WCOTF) on development of WP112, a prodrug of 2-DG that may have therapeutic potential in COVID-19 since 2-DG inhibits glycolysis which prevents the coronavirus from replicating. In its normal state, though, it is metabolized too quickly to be effective. WP112 is only metabolized once it is inside the cell, enabling much higher tissue and organ concentrations of 2-DG.

CNS Pharma up 22% premarket on 2-DG action against coronavirus (NASDAQ:CNSP) | Seeking Alpha
https://seekingalpha.com/news/3560100-cns-pharma-up-22-premarket-on-2-dg-action-against-coronavirus

　

CNS Pharmaceuticals Announces Independent University Research Confirms Active Compound in WP1122 Completely Prevents Coronavirus Replication In Vitro; WP1122 is Subject to Development Agreement with WPD Pharmaceuticals
CNS Pharmaceuticals to receive 50% of net sales on resulting anti-viral commercial products, including WP1122, in certain international markets

HOUSTON, April 13, 2020 /PRNewswire/ -- CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biotechnology company specializing in the development of novel treatments for brain tumors, announced that independent research by the University of Frankfurt found 2-deoxy-D-glucose ("2-DG") to reduce replication of SARS-CoV-2, the virus that causes COVID-19, by 100% in in vitro testing.

Researchers at the University of Frankfurt disclosed the findings in their article submitted to NatureResearch on March 11, 2020 (Bojkova, D et al; DOI: 10.21203/rs.3.rs-17218/v1) (https://www.researchsquare.com/article/rs-17218/v1). The authors reported that inhibiting glycolysis with non-toxic concentrations of 2-DG completely prevented SARS-CoV–2 replication in Caco–2 cells. Glycolysis is a process by which cells convert glucose into energy and infected (host) cells are induced by viruses to dramatically increase their dependence on glycolysis. 2-DG inhibits glycolysis because, although it appears to cells to be glucose, it is in fact a decoy that cannot be converted into energy.

As previously announced, CNS entered into an agreement with WPD Pharmaceuticals Inc. (CSE: WBIO), for the development of several preclinical drug candidates including WP1122. WP1122, which is being tested on a range of viruses including the coronavirus SARS-CoV-2, is a prodrug of the glucose decoy called 2-deoxy-D-glucose, or 2-DG. While the free form of 2-DG is rapidly metabolized and ineffective within minutes of entering the body, WP1122 has a much longer half-life, potentially enabling it to deliver quantities adequate for a therapeutic effect. WPD Pharmaceuticals previously licensed rights to a portfolio of drug candidates, including WP1122, from Moleculin Biotech, Inc. for certain territories.

CNS Pharmaceuticals Announces Independent University Research Confirms Active Compound in WP1122 Completely Prevents Coronavirus Replication In Vitro; WP1122 is Subject to Development Agreement with WPD Pharmaceuticals
https://www.prnewswire.com/news-releases/cns-pharmaceuticals-announces-independent-university-research-confirms-active-compound-in-wp1122-completely-prevents-coronavirus-replication-in-vitro-wp1122-is-subject-to-development-agreement-with-wpd-pharmaceuticals-301039193.html