dichloroacetate

Dichloroacetate (DCA) is a small molecule analogue of acetic acid in which two hydrogen atoms of the methyl group are replaced by chlorine atoms. It acts primarily as an inhibitor of pyruvate dehydrogenase kinase (PDK), thereby activating the mitochondrial pyruvate dehydrogenase complex and shifting cellular metabolism from glycolysis to oxidative phosphorylation. This mechanism has been explored for therapeutic applications in inherited mitochondrial disorders causing lactic acidosis, pulmonary hypertension, and various solid tumors—particularly due to its ability to reverse the Warburg effect in cancer cells and promote apoptosis through increased oxidative stress and reduced lactate levels. DCA has also been used experimentally for metabolic diseases such as diabetes mellitus and dyslipidemia by stimulating glucose utilization and inhibiting gluconeogenesis. The main limiting toxicity is reversible peripheral neuropathy; other toxicities include hepatotoxicity at high doses in animal models. DCA was previously approved in Canada as a topical agent for warts but is not currently approved for systemic use[1][2][4][5][6].

Other names

dichloroacetatedichloroacetic acidbichloroacetic acidBCA