Diisopropylamine dichloroacetate
Diisopropylamine dichloroacetate is the diisopropylamine salt of dichloroacetic acid. It has been marketed in Japan under the trade name Liverall for the treatment of chronic liver conditions, including fatty liver and hepatitis. In laboratory studies, DADA has demonstrated activity as a pyruvate dehydrogenase kinase 4 inhibitor. In a 2014 animal model of severe influenza, oral administration of DADA restored pyruvate dehydrogenase activity, improved ATP production, and significantly increased survival. The compound has also been cited in equine sports medicine due to its metabolism to diisopropylamine, a known vasodilator prohibited in race horses.
Chemistry and background
DADA is formed by combining diisopropylamine with dichloroacetic acid. It is chemically related to pangamic acid, which may convert to DADA and diisopropylamine in the body.Pharmacology
DADA functions primarily as an inhibitor of pyruvate dehydrogenase kinase 4, which regulates the pyruvate dehydrogenase complex that links glycolysis and mitochondrial oxidative phosphorylation. In preclinical mouse models of H1N1 influenza infection, DADA restored down‑regulated pyruvate dehydrogenase activity, increased ATP production in key organs, suppressed cytokine storm, and improved survival rates.In vitro studies on cancer cell lines—including non‑small cell lung carcinoma —demonstrated that DADA induces apoptosis, reduces lactate production, and alters tumor metabolic profiles, with synergistic effects when used alongside chemotherapy or radiotherapy.
Pharmacokinetic data from equine and human studies indicate that DADA is rapidly absorbed and metabolized to diisopropylamine and dichloroacetate, with delayed elimination following chronic dosing. It is well-tolerated in both species at therapeutic doses, although detailed human safety profiles remain limited.
History
DADA was first identified in 1951 as a component of pangamic acid isolated from apricot seeds, and became available for clinical investigation in the 1960s for hepatoprotective properties. It was marketed in Japan under brand names such as Liverall for chronic liver disorders, including fatty liver and hepatitis.In the 1980s, researchers explored DADA's vasodilatory effects and metabolism to DIPA in equine and human subjects. A study published in 1988 monitored pharmacokinetics and behavioral outcomes in horses and noted agricultural and performance interests.
More recently, the compound has gained scientific interest due to its metabolic regulatory mechanisms. A 2014 PLoS ONE study by Yamane et al. demonstrated its efficacy in treating severe influenza in mice via PDK4 inhibition. Since then, DADA has attracted attention in oncology research for its tumor‑metabolism targeting capabilities and is currently under exploration for its synergistic potential in cancer therapy.