Lonidamine | Inhibits Cancer Cell Metabolism

Lonidamine (50264-69-2) was originally investigated as an antispermatogenic agent.¹ Lonidamine has been shown to decrease oxygen consumption as well as aerobic and anaerobic glycolysis in tumor cells leading to apoptosis.² These effects have been attributed to the ability of lonidamine to inhibit mitochondrially bound hexokinase (IC₅₀ = 90 μM for aerobic glycolysis, 45 μM for anaerobic glycolysis using Ehrlich ascites tumor cells)². The apoptotic/antineoplastic effects of lonidamine have also been attributed to its ability to disrupt the mitochondrial transmembrane potential³ , intracellular acidification by inhibition of lactate efflux⁴ , and inhibition of the mitochondrial pyruvate carrier (MPC) and monocarboxylate transporter (MCT)⁵.

References/Citations
1) Gatto et al. (2002), Recent studies on lonidamine, the lead compound of the antispermatogenic indazol-carboxylic acids; Contraception, 65 277
2) Floridi et al., (1981), Effect of Lonidamine on the Energy Metabolism of Ehrlich Ascites Tumor Cells; Cancer Res., 41 4661
3) Ravagnan et al. (1999), Lonidamine triggers apoptosis via a direct, Bcl-2-inhibited effect on the mitochondrial permeability transition pore; Oncogene, 18 2537
4) Ben-Horin et al. (1995), Mechanism of Action of the Antineoplastic Drug Lonidamine: 31P and 13C Nuclear Magnetic Resonance Studies; Cancer Res. 55 2814
5) Nath et al. (2016), Mechanism of antineoplastic activity of lonidamine; Biochim.Biophys.Acta Reviews on Cancer 1866 151