2-deoxy-d-glucose

**2-deoxy-d-glucose (2-DG)** is a synthetic glucose analog in which the hydroxyl group at the second carbon is replaced by hydrogen. This modification prevents it from undergoing further glycolysis after phosphorylation. As a result, it acts as a competitive inhibitor of glycolysis by blocking enzymes such as hexokinase and phosphoglucoisomerase. The drug accumulates intracellularly as 2-deoxyglucose-6-phosphate and disrupts ATP production and cell survival—especially in hypoxic tumor cells that rely on anaerobic glycolysis for energy[1][4][5][6]. Therapeutically, it has been investigated primarily as an adjunct to chemotherapy and radiotherapy for solid tumors (including lung, breast, pancreas, head/neck, and gastric cancers), exploiting its ability to sensitize cancer cells to cytotoxic treatments[1][4]. It has also been studied for antiviral effects (notably against herpes simplex virus) due to interference with viral replication pathways[1]. In May 2021 in India, emergency use authorization was granted for moderate-to-severe COVID-19 based on evidence suggesting faster recovery and reduced oxygen dependence[8][2]. Mechanistically beyond glycolysis inhibition, it can also inhibit N-glycosylation processes due to its structural similarity with mannose—inducing ER stress responses in mammalian cells[5]. Diagnostic applications include use of radiolabeled forms (e.g., fluorine-18) in PET imaging to assess tissue glucose metabolism.

Other names

2-deoxyglucose2-DG2-deoxy-d-arabino-hexopyranose