Lonidamine (AF-1890)

Description: Lonidamine (AF 1890, Diclondazolic Acid) is an orally bioactive small molecule inhibitor of hexokinase, also inhibits mitochondrial pyruvate carrier (Ki 2.5 uM in isolated rat liver mitochondria) and plasma membrane monocarboxylate transporters. Lonidamine reduces the oxygen consumption in both normal and neoplastic cells, while it increases the aerobic glycolysis of normal cells but inhibited that of tumor cells. Lonidamine induces the permeabilization of ANT proteoliposomes in a cell-free system, yet has no effect on protein-free liposomes. Lonidamine adds to synthetic planar lipid bilayers containing ANT, eliciting ANT channel activities with clearly distinct conductance levels. Lonidamine provokes a disruption of the mitochondrial transmembrane potential which precedes signs of nuclear apoptosis and cytolysis.

References: J Natl Cancer Inst. 1981 Mar; 66(3):497-9; Oncogene. 2001 Nov 15; 20(52):7579-87; J Natl Cancer Inst. 1998 Sep 16; 90(18):1400-6.