Research Area: Cancer
Biological Activity:
Lonidamine is an orally administered small molecule hexokinase inactivator with an IC50 of 0.85 mM. Lonidamine inhibits glycolysis by the inactivation of hexokinase. Interestingly, Lonidamine seems to enhance aerobic glycolysis in normal cells, but suppress glycolysis in cancer cells. This is most likely through the inhibition of the mitochondrially bound hexokinase. Lonidamine inhibits both respiration and glycolysis leading to a decrease in cellular ATP. In addition, lonidamine may increase programmed cell death. This stems from the observation that mitochondria and mitochondria-bound hexokinase are crucial for induction of apoptosis. In vitro models with lonidamine exhibit the hallmarks of apoptosis, including mitochondrial membrane depolarization, release of cytochrome C, phosphatidylserine externalization, and DNA fragmentation. Lonidamine also blocks CFTR Cl- channels in vitro. [1][2][3][4]References on Lonidamine[1] http://en.wikipedia.org/wiki/Lonidamine, , [2] Mol Biochem Parasitol., 2008 Apr, 158(2):202-7[3] Cancer Chemother Pharmacol. , 1989, 25(1):32-6[4] Rev Urol. , 2005, 7 Suppl 7:S21-6 |