2DeoxyDglucose

2-deoxy-D-glucose (2-DG) is a glucose analog in which the hydroxyl group on carbon-2 is replaced by hydrogen, giving the chemical formula C6H12O5. The molecule is taken up by glucose transporters (GLUT family) and phosphorylated by hexokinase to 2-deoxy-D-glucose-6-phosphate (2-DG-6-P); however, unlike glucose-6-phosphate, 2-DG-6-P is not efficiently metabolized through glycolysis because it is a poor substrate for phosphoglucose isomerase. The accumulation of 2-DG-6-P inhibits glycolysis, lowering cellular ATP production, and can cause metabolic stress. In addition, 2-DG can interfere with N-linked glycosylation, contributing to misfolded glycoproteins and endoplasmic reticulum stress.

Uses in research include probing glucose metabolism and sensitizing cells to therapy in cancer models. It is commonly used in in vitro experiments and animal studies to study metabolic pathways and cellular stress responses. In clinical imaging contexts, a related tracer, 18F-fluorodeoxyglucose (FDG), is widely used for positron emission tomography; 2-DG itself is not a routine diagnostic imaging agent in humans, though radiolabeled derivatives have been explored in research settings.

Clinical status and safety considerations: 2-DG has been investigated in clinical trials as an adjunct to cancer therapy but is not approved as a general cancer treatment due to variable efficacy and safety concerns. Reported adverse effects include hypoglycemia, fatigue, and gastrointestinal symptoms, and its use requires careful metabolic monitoring. As a result, 2-DG remains primarily a research tool rather than an approved medical therapy.