Diisopropylamine Dichloroacetate

DADA is diisopropylamine dichloroacetate, the 1:1 salt of the base diisopropylamine and dichloroacetic acid (PubChem CID 12617). Its anion is dichloroacetate, the same anion as in sodium dichloroacetate (DCA), a classic inhibitor of pyruvate dehydrogenase kinase (PDK). These kinases downregulate the mitochondrial pyruvate dehydrogenase complex by phosphorylating it (Kato et al., 2007), and in recombinant enzyme assays DADA inhibited PDK4 and PDK2 at concentrations close to those of DCA (Yamane et al., 2014).

PubChem CID 12617 lists the same formula and weight and is the source of the aliases and the two-component structure. Dichloroacetic acid accounts for 128.94 of the 230.13 g/mol, about 56% of the salt's mass.

A PubMed search for "diisopropylamine dichloroacetate" returned 80 records on 13 October 2026. The first area sorts them by model.

What the 80 PubMed records cover

The search also matches the substance's indexing concept, which PubMed has attached to some papers that use the abbreviation DIPA for other things. Sorted by model:

• 38 records from 1960 to 1966 (34 in Italian), when the salt was called DIEDI or IS-401, none with a PubMed abstract. Their titles cover general pharmacology, animal and tissue models (for example burn shock, pulmonary edema, retinal injury, bone repair and viral infection) and clinical observations in circulatory, eye and other conditions.
• 9 Russian-language clinical reports and reviews from 1982 to 1995, most using the name dipromonium.
• 7 other records from 1971 to 1999: six laboratory or animal studies (guinea pig ileum, the Ames bacterial mutagenicity test, rat organs, horses, rat hepatocytes and human keratinocytes) and one paper titled "Legal aspects of specious dietary claims".
• 4 records from 2014 to 2024 that use it as a PDK4 inhibitor or metabolic tool compound in rodent models of influenza, colitis and experimental autoimmune encephalomyelitis, or review that work.
• 7 records from 2015 to 2026 that use tumor cell lines or tumor-bearing mice.
• 3 Chinese records from 2005 to 2008 on fatty liver disease: an article on drug therapy, a rat model with the salt as a comparison group, and a clinical trial.
• 12 that do not study the salt: 9 use DIPA or dIPA for something else, such as a gene-editing method or a pain scale, 1 does not mention the salt in its abstract, and 2 concern diisopropylamine alone.

Dichloroacetate and pyruvate dehydrogenase kinase

In crystal structures of human PDK1, dichloroacetate bound in the helix bundle of the N-terminal domain and caused conformational changes that the authors linked to inactivation of the kinase (Kato et al., 2007). With recombinant human kinases, DADA's half-maximal inhibitory concentrations were 50.9 µM for PDK4 and 636.0 µM for PDK2, close to sodium dichloroacetate's 57.8 and 676.0 µM in the same assays (Yamane et al., 2014).

In normal human keratinocytes, DADA increased cell growth and two differentiation markers, and when each component was tested separately, dichloroacetate was active and diisopropylamine was not (Kitamura et al., 1999). Dichloroacetate also forms during water chlorination and is dehalogenated in vivo to monochloroacetate and glyoxylate (Stacpoole et al., 1998). Models: purified proteins, enzyme assays and keratinocyte culture.

Infection and inflammation models (mouse)

In mice infected with influenza A/PR/8/34 (H1N1), infection lowered pyruvate dehydrogenase activity and ATP and raised PDK4 in several organs, including skeletal muscle, heart and lungs. DADA given by mouth every 12 hours for 14 days from infection restored pyruvate dehydrogenase activity and ATP in various organs, and the authors reported higher survival with lower cytokine levels and viral replication (Yamane et al., 2014).

The compound came from Daiichi Sankyo Healthcare, which employed two authors; five authors are inventors on a related patent application. In mice with experimental autoimmune encephalomyelitis, DADA alone did not change disability scores, while DADA with melatonin lowered them compared with melatonin alone and restored pyruvate dehydrogenase complex function that melatonin had reduced (Ghareghani et al., 2022). Models: mice.

Detection and mutagenicity testing

In Thoroughbred and Standardbred horses, diisopropylamine, the base half of the salt, was the major metabolite in urine; the authors developed a thin-layer chromatography screen and a gas chromatography assay with a lower limit of detection of 0.5 µg/mL of urine, and neither form was detectable in blood by those methods (Yang et al., 1988). In the Ames Salmonella/mammalian microsome test, both diisopropylamine dichloroacetate and diisopropylamine were mutagenic (Gelernt and Herbert, 1982), and dichloroacetate showed low-grade mutagenicity (Herbert et al., 1980). Models: horses and a bacterial reverse-mutation assay.

Human studies (research history)

The Russian-language reports mostly use the name dipromonium, which one called a derivative of pangamic acid (Markova, 1990), in dermatology, pulmonary tuberculosis, hypertension and multiple sclerosis. A multicenter randomized double-blind trial in China assigned 127 patients with nonalcoholic fatty liver disease to one of two daily amounts for 8 weeks and recorded symptoms, serum ALT, serum lipids and ultrasound grading (Lu et al., 2005). None of these studies tested the material sold here.