Brain tumor cells depend on glycolysis for their metabolism of glucose to produce energy.

These metabolic tumor cell dependence requires approximately 18 times more glucose than a normal cell to produce the same amount of energy. This led to the theory that if tumor cells are fed a “glucose decoy” (one that can’t convert into energy) to block specific tumor glucose metabolism, we can “starve” (kill) the tumor. 2-Deoxyglucose (2- DG) has been used as a decoy, but studies demonstrated that it does not have druglike properties. To improve pharmacokinetics and increase specific organ and tumor uptake a new prodrug was designed. WP1122 is a prodrug of 2-DG that increases half-life, enables higher uptake by the brain and overall improves drug-like properties. In brain tumor models WP1122 performs as well or better than temozolomide; even better performance was shown by combining the two drugs. Additional studies demonstrated a high uptake of the drug by pancreas clearly indicating on a unique opportunity to target highly glycolytic by its nature pancreatic cancer.