2DG-ODDA is a potent antitumor derivative of 2-deoxyglucose (2-DG). It induces apoptosis and reduces ATP production. 2DG-ODDA is absorbed via fatty acid and glucose transporters and cleaved by α-Mannosidase to release 2DG, thereby inhibiting N-glycosylation and disrupting cellular metabolism. It suppresses tumor growth in 4T1 murine models and is applicable in triple-negative breast cancer (TNBC) research.

2DG-ODDA significantly reduces glycolytic, mitochondrial, and total ATP production in 4T1 TNBC cells at a concentration of 80 μM for 24 hours, indicating its dual impact on glycolysis and mitochondrial metabolism. At 400 μM for 24 hours, it induces apoptosis in 4T1 triple-negative breast cancer cells. The compound also exhibits cytotoxicity against 4T1 TNBC cells, with an IC50 of approximately 85 μM, which is 16 times more potent than 2DG (IC50 = ~1.34 mM). At 85 μM for 24 hours, 2DG-ODDA is taken up via CD36 (fatty acid transporter) and glucose transporters, cleaved by α-Mannosidase to release 2DG, thereby inhibiting N-glycosylation and disrupting cellular metabolism.

Administered 2DG-ODDA (7.5 mg/kg; subcutaneous injection; three times weekly for two weeks) suppresses tumor growth in a 4T1 triple-negative breast cancer mouse model.