DADA (Diisopropylamine Dichloroacetate)

DADA (Diisopropylamine Dichloroacetate)

DADA (Diisopropylamine Dichloroacetate)

DADA (Diisopropylamine Dichloroacetate)

DADA (Diisopropylamine Dichloroacetate / Diisopropylammonium Dichloroacetate) is a 1:1 dichloroacetate salt and pyruvate dehydrogenase kinase (PDK) inhibitor for mitochondrial and oxidative metabolism research. By inhibiting PDK, DADA keeps the pyruvate dehydrogenase (PDH) complex in its active, dephosphorylated state, favoring pyruvate oxidation to acetyl-CoA over lactate formation. CAS 660-27-5.

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Chemical and Molecular Data

What is DADA (Diisopropylamine Dichloroacetate)?

DADA (diisopropylamine dichloroacetate, also called diisopropylammonium dichloroacetate or DIPA-DCA; CAS 660-27-5) is a 1:1 salt of diisopropylamine and dichloroacetic acid. It is a small-molecule inhibitor of pyruvate dehydrogenase kinase (PDK), the mitochondrial enzyme that switches the pyruvate dehydrogenase complex (PDC) off by phosphorylation. DADA is not a peptide and not an amino acid, even though many searches call it a “DADA peptide.” Its activity comes from the dichloroacetate anion, which binds a regulatory pocket on PDK and holds the kinase in an inactive shape.

In recombinant kinase assays, DADA inhibited recombinant PDK4 with an IC50 of 50.9 µM and PDK2 with an IC50 of 636.0 µM, nearly matching sodium dichloroacetate under the same conditions (Yamane et al., 2014, PMC4035290). That is what DADA does at the enzyme level: it keeps PDC in its active, dephosphorylated state, so pyruvate keeps flowing toward acetyl-CoA.

Batch-verified at Modern Aminos, DADA is supplied in three laboratory formats:

  • 200 mg/mL solution, 20 mL glass vial (Form option “20ML”)
  • 250 mg dry-fill capsules, 60 units per bottle (Form option “250MG Dry-Fill”)
  • 300 mg/mL solution, 30 mL amber glass bottle with a 1 mL precision dropper (Form option “300MG/ML 30ML”)

Laboratories building mitochondrial and metabolic assay panels often place DADA next to other public reference listings such as ITPP (myo-inositol trispyrophosphate) and GC-1 (Sobetirome), as well as SLU-PP-332, BAM15, AICAR, and MOTS-C. For a closer look at the ERR agonist pair, see SLU-PP-332 vs SLU-PP-915.

Chemical and Molecular Data for DADA (Diisopropylamine Dichloroacetate)

Compound Name DADA (Diisopropylamine Dichloroacetate)
Research Category Pyruvate dehydrogenase kinase (PDK) inhibitor; dichloroacetate salt; mitochondrial metabolism reference compound
Quantity / Formats Offered 200 mg/mL Solution (20 mL Vial) | 250 mg Dry-Fill Capsules (60 Units) | 300 mg/mL Solution (30 mL Dropper Bottle)
Synonyms / Alt Names Diisopropylammonium dichloroacetate, diisopropylamine 2,2-dichloroacetate, DIPA-DCA, DADA, dichloroacetic acid diisopropylamine salt, IS-401; historically associated with “pangamic acid” (B15) preparations
CAS Number 660-27-5
PubChem CID 12617
ChEBI ID CHEBI:31492
UNII / EC Number BA6QDP0R4E / 211-538-2
Chemical Formula C8H17Cl2NO2 (C6H15N · C2H2Cl2O2)
Molecular Weight 230.13 g/mol (salt); components: diisopropylamine 101.19 g/mol, dichloroacetic acid 128.94 g/mol
Exact Mass 229.0636 Da
Stoichiometry 1:1 ammonium carboxylate salt (diisopropylammonium cation · dichloroacetate anion)
IUPAC Name 2,2-dichloroacetic acid; N-propan-2-ylpropan-2-amine
InChIKey ILKBHIBYKSHTKQ-UHFFFAOYSA-N
SMILES Code CC(C)NC(C)C.C(C(=O)O)(Cl)Cl (ionic form: CC(C)[NH2+]C(C)C.C(C(=O)[O-])(Cl)Cl)

Identity fields are drawn from PubChem CID 12617 and ChEBI; purity and quantity values come from the lot certificates in the Certificate of Analysis tab.

What are the Mechanisms of Action?

The biochemical targets and pathway logic of DADA in laboratory research include:

  • Pyruvate Dehydrogenase Kinase (PDK) Inhibition: Dichloroacetate is a synthetic pyruvate analog. Crystal structures show it binding the pyruvate site in the center of the N-terminal regulatory (R) domain of PDK2 (Knoechel et al., 2006) and the helix bundle of the PDK1 N-terminal domain, where it triggers conformational changes that reach both the nucleotide-binding and lipoyl-binding pockets and switch the kinase off (Kato et al., 2007). In classic enzyme kinetics the inhibition was mainly non-competitive with respect to ATP (Whitehouse, Cooper & Randle, 1974).
  • Isoform Selectivity Across PDK1–PDK4: The four PDK isoenzymes differ sharply in their sensitivity to dichloroacetate. Apparent Ki values range about 40-fold, from 0.2 mM for PDK2 to 8 mM for PDK3 (Bowker-Kinley et al., 1998). In a recombinant kinase panel, DADA was about 12.5-fold more potent against PDK4 than PDK2 (Yamane et al., 2014).
  • The DW-Motif Signaling Network: Site-directed mutagenesis of PDK2 showed that the invariant C-terminal DW-motif (Asp-382, Trp-383) relays the signal from the DCA-binding site to the nucleotide and lipoyl-domain sites, locking the kinase in an inactive “closed” conformation (Li, Kato & Chuang, 2009).
  • Pyruvate Flux & Lactate Formation: With PDK held off, the E1α subunit of PDC stays dephosphorylated and active, so pyruvate is decarboxylated to acetyl-CoA for the Krebs cycle rather than reduced to lactate by lactate dehydrogenase (LDH). This is why PDK inhibitors appear in mitochondrial respiration, glucose oxidation, and lactate/pyruvate ratio assay menus.
  • Diisopropylammonium Counter-Ion Chemistry: Diisopropylamine is a secondary amine base. Pairing it with dichloroacetic acid, a strong carboxylic acid, gives a stable 1:1 ammonium carboxylate salt. The counter-ion sets the salt’s mass (230.13 g/mol versus 128.94 g/mol for the free acid), which matters when matching molar concentrations against sodium dichloroacetate standards.
Assay Parameter DADA Dichloroacetate (DCA) Source
IC50, PDK4 (recombinant) 50.9 µM 57.8 µM Yamane 2014, Table 3
IC50, PDK2 (recombinant) 636.0 µM 676.0 µM Yamane 2014, Table 3
Apparent Ki, PDK2 to PDK3 not reported 0.2 mM (PDK2) to 8 mM (PDK3) Bowker-Kinley 1998
Binding site Dichloroacetate anion (same pharmacophore) Pyruvate site, N-terminal regulatory domain Knoechel 2006; Kato 2007

What Does Published Research Show for DADA?

Peer-reviewed literature on DADA (Diisopropylamine Dichloroacetate) and its active dichloroacetate anion centers on enzyme kinetics, structural biology, and pathway regulation:

  • Direct PDK4 and PDK2 Kinetics (PMC): A recombinant kinase panel run by off-chip mobility shift assay reported DADA IC50 values of 50.9 µM (PDK4) and 636.0 µM (PDK2), essentially the same as sodium dichloroacetate tested alongside it. This is the main published source naming DADA itself as a PDK4-preferring inhibitor (PMC4035290).
  • Structural Biology of the DCA Site (PubMed / PMC): Crystal structures of PDK2 (PubMed 16401071) and PDK1/PDK3 (PubMed 17683942) locate dichloroacetate in the N-terminal regulatory domain, separate from the ATP pocket targeted by radicicol and the lipoyl pocket targeted by AZD7545.
  • Isoform Kinetics (PMC): Kinetic parameters for the four PDK isoenzymes showed 25-fold differences in specific activity and 40-fold differences in dichloroacetate Ki between isoforms (PMC1219031).
  • Founding Mechanism Work (PMC): The 1974 Biochemical Journal study established that dichloroacetate and related halogenated acids inhibit PDK rather than stimulating PDC directly, and that it had no significant effect on PDC phosphatase (PMC1168183).
  • Chemical Directory & Structure Verification (PubChem / ChEBI): PubChem CID 12617 and ChEBI 31492 list the 230.13 g/mol mass, 1:1 salt composition, and InChIKey ILKBHIBYKSHTKQ-UHFFFAOYSA-N for CAS 660-27-5.
  • Analytical Quality: Why chromatographic testing matters for reference materials is covered in Modern Aminos’ note on HPLC testing.

How does DADA compare to other compounds?

To map metabolic pathways, mitochondrial targets, and respiration mechanics, researchers compare DADA against other metabolic reference compounds, including several available at Modern Aminos:

Compound / Reference Primary Target Class Core Mechanism of Action Research Focus & Profile
DADA (Diisopropylamine Dichloroacetate) Pyruvate Dehydrogenase Kinase (PDK) Inhibitor Salt Dichloroacetate anion binds the PDK regulatory domain, keeping the PDH complex dephosphorylated and active Pyruvate oxidation, lactate/pyruvate ratios, PDK isoform selectivity (PDK4 > PDK2), mitochondrial respiration assays
Sodium Dichloroacetate (DCA) PDK Inhibitor (sodium salt) Same dichloroacetate pharmacophore as DADA, paired with a sodium counter-ion Reference standard for PDK kinetics; nearly identical PDK2/PDK4 IC50 values to DADA
SLU-PP-332 (comparison guide) Pan-ERR Nuclear Receptor Agonist Binds ERRα/β/γ to recruit PGC-1α and upregulate mitochondrial OXPHOS gene networks Nuclear receptor-driven transcription of mitochondrial biogenesis genes; acts upstream of enzyme regulation
BAM15 Mitochondrial Protonophore Uncoupler Carries protons across the inner mitochondrial membrane, uncoupling oxidative phosphorylation from ATP synthesis Uncoupling and oxygen consumption rate (OCR) assays; selective for mitochondrial over plasma membranes
AICAR AMPK Agonist Converted to ZMP, an AMP mimic that activates AMP-activated protein kinase (AMPK) independent of cellular ATP levels Energy-sensing kinase signaling, glucose uptake pathways, and mitochondrial biogenesis signaling
ITPP Allosteric Effector of Hemoglobin Binds the central cavity of hemoglobin and right-shifts the oxygen dissociation curve (raises P50) Oxygen-delivery chemistry, a supply-side complement to DADA’s enzyme-side PDH regulation
GC-1 (Sobetirome) Thyroid Hormone Receptor β (TRβ) Agonist Subtype-selective TRβ1 agonist acting on nuclear transcription Lipid-metabolism gene regulation; transcriptional, not enzymatic, control point

Frequently Asked Questions (FAQs)

1. Is Modern Aminos a reliable place to buy DADA (Diisopropylamine Dichloroacetate)?

Modern Aminos publishes third-party certificates from Vanguard Laboratory, an A2LA-accredited lab, for DADA. The raw powder lists chromatographic purity above 99.50% (± 0.18%) by LC-MS/MS, the 250 mg dry-fill capsules list per-unit HPLC quantity values of 248.65, 235.96, and 248.79 mg, the 300 mg/mL solution lists 305 mg/mL by HPLC, and the 20 mL vial lists a USP <71> sterility pass. If you want to buy diisopropylamine dichloroacetate as a documented reference material, each certificate is in the Certificate of Analysis tab.

2. Is DADA a peptide or an amino acid?

No. Even though it is often searched as “DADA peptide” or “DADA amino,” DADA has no amide-linked amino acid chain and no amino acid in its structure. It is a small-molecule salt (230.13 g/mol) made of one diisopropylamine cation and one dichloroacetate anion. It is grouped with peptide catalogs only because many research suppliers list both.

3. Is DADA a supplement or a research chemical?

Modern Aminos lists DADA as a research chemical: a defined compound with CAS number 660-27-5, PubChem CID 12617, and a characterized PDK-inhibition profile. The “DADA supplement” label comes from old “pangamic acid” products, not from any recognized vitamin or nutrient.

4. What is the molecular target and primary function of DADA (Diisopropylamine Dichloroacetate)?

DADA targets pyruvate dehydrogenase kinase (PDK) inside the mitochondrial matrix. By inhibiting PDK, it prevents the inhibitory phosphorylation of the pyruvate dehydrogenase complex, keeping that complex active so it converts glycolytic pyruvate into acetyl-CoA. In recombinant kinase assays, DADA’s IC50 was 50.9 µM for PDK4 and 636.0 µM for PDK2.

5. How does PDK inhibition change glucose and pyruvate metabolism?

PDK phosphorylates the E1α subunit of the pyruvate dehydrogenase complex and turns it off. When PDK is inhibited, the complex stays active, so pyruvate from glycolysis is oxidized to acetyl-CoA and fed into the Krebs cycle and oxidative phosphorylation instead of being reduced to lactate by lactate dehydrogenase (LDH). In assay terms, that means a higher oxygen consumption rate and a lower lactate-to-pyruvate ratio.

6. What role does the diisopropylamine moiety play alongside dichloroacetate?

Diisopropylamine is the counter-ion. As a secondary amine base, it neutralizes dichloroacetic acid to form a stable, weighable 1:1 diisopropylammonium salt. In side-by-side PDK2 and PDK4 kinase assays, DADA and sodium dichloroacetate gave nearly identical IC50 values, which indicates that the dichloroacetate anion carries the PDK activity while the amine mainly sets the salt’s mass and physical form.

7. How is DADA different from DCA (sodium dichloroacetate)?

Both deliver the same dichloroacetate anion; only the partner ion differs. DADA pairs it with diisopropylammonium (230.13 g/mol for the salt), and DCA research standards usually pair it with sodium. Because the counter-ions have different masses, equal weights of the two salts do not hold equal moles of dichloroacetate. Molar concentration is the fair basis for comparison.

8. Is DADA the same as pangamic acid (“vitamin B15”)?

No. “Pangamic acid” was a mid-20th-century trade label, and DADA was sold in preparations carrying that name, which is why the PubChem synonym list for CAS 660-27-5 still includes B15-era product names. Chemically, DADA is simply diisopropylamine dichloroacetate, and “B15” is not a recognized vitamin.

9. What available formats does Modern Aminos offer for DADA research?

Modern Aminos supplies DADA in three formats: a 200 mg/mL solution in a 20 mL glass vial, 250 mg dry-fill capsules (60 units per bottle), and a 300 mg/mL solution in a 30 mL amber glass bottle with a 1 mL precision dropper. A loose DADA powder format is not offered. “DADA powder” on a certificate refers to the raw material tested before filling.

10. How does DADA compare to BAM15 or SLU-PP-332 in metabolic assays?

They act at three different control points. BAM15 is a mitochondrial protonophore that uncouples oxidative phosphorylation from ATP synthesis. SLU-PP-332 is an estrogen-related receptor (ERR) agonist that upregulates mitochondrial gene transcription. DADA acts directly on an enzyme switch, inhibiting PDK to keep pyruvate flowing through the pyruvate dehydrogenase complex. See our SLU-PP-332 vs SLU-PP-915 comparison for the ERR side of that map.

11. How does Modern Aminos verify the chemical identity and purity of DADA?

The raw powder is checked by LC-MS/MS. The certificate shows a multiple-reaction-monitoring trace for the diisopropylamine ion (102.2 → 60.0 Da) and reports chromatographic purity above 99.50% (± 0.18%). Finished formats then get their own tests: HPLC-UV/VIS quantity per capsule and per mL of solution, and USP <71> sterility for the 20 mL vial.

12. What are the proper storage protocols for DADA formulations?

Keep capsule bottles, vials, and dropper bottles tightly sealed in a cool, dry place (15 °C to 25 °C), away from direct light, heat, and moisture. Follow the label on each lot for its specific storage note.

Capsule products are not intended for time-release and are for transport only.

DISCLAIMER: All compounds and research materials provided by Modern Aminos are strictly for laboratory and research use only. They are not approved for human consumption by the Food and Drug Administration (FDA). No products are approved for oral, sublingual, nor in vivo use. These products should not be used for any form of in vivo experimentation or for any other non-laboratory purpose. Any violation or indication of human or animal use will result in immediate removal from being able to purchase products in the future. By purchasing these products, you acknowledge that they will be used exclusively within a controlled and qualified research environment.

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