Lonidamine

Lonidamine is an orally administered small molecule hexokinase inactivator, an anticancer and antispermatogenic agent in vitro and in vivo. Lonidamine inhibits cellular energy metabolism in some cells via inhibition of mitochondrial hexokinase. It also blocks CFTR Cl- channels in vitro. Lonidamine could reduce the dose of temozolomide required for radiosensitization of brain tumours. Lonidamine elicits ERK and Akt/mTOR pathway activation, as indicated by increased ERK, Akt, p70S6K and rpS6 phosphorylation, and these effects are reduced by co-treatment with the anti-leukemic agent arsenic trioxide. Lonidamine significantly extends both median and maximum lifespan of C. elegans when applied at a concentration of 5 micromolar by 8% each. Lonidamine, a dechlorinate derivative of indazole-3-carboxylic acid, has proved to exert a powerful antiproliferative effect and to impair the energy metabolism of neoplastic cells.