3-BrOP is a cell-permeable ester of the the glycolysis inhibitor 3-bromopyruvate (3-BrPA) that is known to target hexokinase II (HK2) and GAPDH. Upon entering the cells, 3-BrOP is hydrolyzed by intracellular esterase to 3-BrPA. 3-BrOP is shown to synergize cancer cell killing with mTOR inhibitor rapamycin (apoptosis induction with/without 100 ng/mL rapamycin = 64%/36% of Raji human lymphoma cells by 40 μM 3-BrOP and 72%/45% of HL-60 leukemia cells by 20 μM 3-BrOP in 24 h) due to enhanced cellular ATP depletion and glucose uptake inhibition. When administered via tail vein injection, 3-BrOP significantly suppersses SK-N-SH xenograft-derived neuroblastoma tumor growth in mice in vivo (by 78% in 14 days; 20 mg/kg/day).
Cell-permeable ester of the the glycolysis inhibitor 3-bromopyruvate (3-BrPA) with in vitro and in vivo anti-cancer efficacy.