dichloroacetate   Click here for help

GtoPdb Ligand ID: 4518

Abbreviated name: DCA
Synonyms: dichloroacetic acid
Compound class: Synthetic organic
Comment: Dichloroacetate (DCA) is an orally available small molecule pyruvate dehydrogenase kinase inhibitor [4]. It acts as a metabolic regulator and has anti-cancer potential by promoting glucose oxidation over glycolysis, glycolysis being the metabolic pathway (Warburg effect) utilised by most cancer cells to resist apoptosis and gain proliferative advantage [1-3].
ChEMBL represents this compound without the charge (see link above).
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 1
Topological polar surface area 40.13
Molecular weight 126.94
XLogP 0.09
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES ClC(C(=O)[O-])Cl
Isomeric SMILES ClC(C(=O)[O-])Cl
InChI InChI=1S/C2H2Cl2O2/c3-1(4)2(5)6/h1H,(H,5,6)/p-1
InChI Key JXTHNDFMNIQAHM-UHFFFAOYSA-M

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Evidence in the literature indicates that dichloroacetate was used to treat inherited mitochondrial disorders that result in lactic acidosis, pulmonary hypertension and several types of solid tumours. However, we can find no proof of marketing authorisations from the FDA, EMA or UK agencies. EMA orphan drug designation for the treatment of systemic monochloroacetate poisoning was withdrawn in 2008 at the request of the sponsor.
There is one ongoing Phase 3 clinical trial in patients with pyruvate dehydrogenase complex deficiency (NCT02616484) registered on ClinicalTrials.gov. An older Phase 2 study for metastatic breast cancer and lung cancer (NCT01029925) was terminated due to higher than expected risk/safety concerns.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01029925 Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or Non-Small Cell Lung Cancer (NSCL) Phase 2 Interventional Jonsson Comprehensive Cancer Center
NCT02616484 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency: Phase 3 Interventional University of Florida