Sodium dichloroacetate

Details

Stereochemistry	ACHIRAL
Molecular Formula	C2HCl2O2.Na
Molecular Weight	150.924
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].[O-]C(=O)C(Cl)Cl

InChI

InChIKey=LUPNKHXLFSSUGS-UHFFFAOYSA-M

InChI=1S/C2H2Cl2O2.Na/c3-1(4)2(5)6;/h1H,(H,5,6);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB08809 | https://www.ncbi.nlm.nih.gov/pubmed/27143230 | http://www.oicc.ca/uploads/dca-health-professional.pdf

Dichloroacetic acid, often abbreviated DCA (dichloroacetate), is an acid analog of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms. The salts and esters of dichloroacetic acid are called dichloroacetates. Salts of DCA are used as drugs since they inhibit the enzyme pyruvate dehydrogenase kinase. Early reports of its activity against brain cancer cells led patients to treat themselves with DCA, which is commercially available in non-pharmaceutical grade. A phase 1 study in 5 patients concluded that DCA was safe, but wasn't designed to establish effectiveness. DCA was approved for use in Canada in 1989 (as a topical formulation for the treatment of warts and for cauterization and removal of a wide variety of skin and tissue lesions), but was cancelled post market. DCA is a noncompetitive inhibitor of the endoplasmic reticulum enzyme HMG CoA reductase, which catalyzes the rate limiting step in cholesterol biosynthesis. DCA has been researched in adults, children, animals, and cells as a monotherapy as well as in combination with other therapies for the treatment of severe metabolic disorders including diabetes and hypercholesterolemia, lactic acidosis, certain heart conditions, and cancer. DCA has been prescribed to reduce tumour size and tumour markers, prevent angiogenesis, reduce cancer related symptoms, manage pain, and aid in palliation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Pyruvate dehydrogenase kinase isoform 2 3 Target ID: CHEMBL3861 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25537215 \| https://www.ncbi.nlm.nih.gov/pubmed/19833728 \| https://www.ncbi.nlm.nih.gov/pubmed/27143230	Inhibitor 8297	0.2 mM [Ki]
Pyruvate dehydrogenase kinase isoform 1 3 Target ID: CHEMBL4766 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17683942	Inhibitor 8297	1.0 mM [Ki]
Pyruvate dehydrogenase kinase isoform 3 3 Target ID: CHEMBL3893 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17683942	Inhibitor 8297	8.0 mM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Pyruvate dehydrogenase complex deficiency 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02616484	Primary	Phase III 656	Unknown Approved Use Unknown
Cancer 592 Sources: http://www.oicc.ca/uploads/dca-health-professional.pdf	Primary	Phase II 1132	Unknown Approved Use Unknown
Congenital lactic acidosis 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00004490	Primary	Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
[Benign infantile mitochondrial myopathy].	2001	11596364
The effect of dichloroacetic acid and trichloroacetic acid on DNA methylation and cell proliferation in B6C3F1 mice.	2001	11284051
Diffusion-weighted image and MR spectroscopic analysis of a case of MELAS with repeated attacks.	2001 Feb	11293491
Effects of dichloroacetate (DCA) on serum insulin levels and insulin-controlled signaling proteins in livers of male B6C3F1 mice.	2001 Jan	11134557
The fate and persistence of trifluoroacetic and chloroacetic acids in pond waters.	2001 Jan	11100931
Study on the cytochrome P-450- and glutathione-dependent biotransformation of trichloroethylene in humans.	2001 Mar	11317702
Dichloroacetate: population pharmacokinetics with a pharmacodynamic sequential link model.	2001 Mar	11269566
Dichloroacetate reduces diaphragmatic lactate formation but impairs respiratory performance.	2001 Nov 1	11719308
Genetic polymorphisms in assessing interindividual variability in delivered dose.	2002 Apr	12052003
An acetyl group deficit limits mitochondrial ATP production at the onset of exercise.	2002 Apr	12023864
Nephrotoxicity of chlorofluoroacetic acid in rats.	2002 Dec	12441371
Measurement of interstitial lactate during hypoxia-induced dilatation in isolated pressurised porcine coronary arteries.	2002 Feb 15	11850519
Oxygen uptake on-kinetics in dog gastrocnemius in situ following activation of pyruvate dehydrogenase by dichloroacetate.	2002 Jan 1	11773328
Solar photodegradation of dichloroacetic acid and 2,4-dichlorophenol using an enhanced photo-Fenton process.	2002 Jul	12152739
Kinetics of the biotransformation of maleylacetone and chlorofluoroacetic acid by polymorphic variants of human glutathione transferase zeta (hGSTZ1-1).	2002 Jul	12119007
Manipulations in glycogen metabolism and the failure to influence infarct size in the ischaemic rabbit heart.	2002 Jul	12113612
Skeletal muscle metabolism is unaffected by DCA infusion and hyperoxia after onset of intense aerobic exercise.	2002 Jul	12067850
Contribution of dichloroacetate and trichloroacetate to liver tumor induction in mice by trichloroethylene.	2002 Jul 1	12127263
Pyruvate dehydrogenase and the regulation of glucose oxidation in hypertrophied rat hearts.	2002 Mar	11922894
Distribution of haloacetic acids in the water columns of the Laurentian Great Lakes and Lake Malawi.	2002 May 1	12026968
The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure.	2002 Nov	12439634
Mass spectral characterization of dichloroacetic acid-modified human glutathione transferase zeta.	2002 Nov	12437329
Stearoyl-CoA desaturase 1 (Scd1) gene overexpression is associated with genetic predisposition to hepatocarcinogenesis in mice and rats.	2002 Nov	12419843
Brief increase in carbohydrate oxidation after reperfusion reverses myocardial stunning in conscious pigs.	2002 Nov 26	12451011
The acetyl group deficit at the onset of contraction in ischaemic canine skeletal muscle.	2002 Oct 15	12381829
Dichloroacetate accelerates the fall in intracellular PO2 at onset of contractions in Xenopus single muscle fibers.	2003 Feb	12446276
A 2-year dose-response study of lesion sequences during hepatocellular carcinogenesis in the male B6C3F(1) mouse given the drinking water chemical dichloroacetic acid.	2003 Jan	12515679
Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart.	2003 Jul	12793977
Formation of chloroacetic acids from soil, humic acid and phenolic moieties.	2003 Jul	12738276
Identification of trichloroethylene and its metabolites in human seminal fluid of workers exposed to trichloroethylene.	2003 Mar	12584157
Regulation of transforming growth factor-beta, type III collagen, and fibronectin by dichloroacetic acid in human fibroblasts from normal peritoneum and adhesions.	2003 May	12738512
Dichloroacetate increases skeletal muscle pyruvate dehydrogenase activity during acute limb ischemia.	2003 May-Jun	12799728
Effects of dichloroacetate on VO2 and intramuscular 31P metabolite kinetics during high-intensity exercise in humans.	2003 Sep	12754181

Patents

Sample Use Guides

In Vivo Use Guide

Brain Cancer treatment: Oral DCA given twice daily for the 24 week period of the study.

Route of Administration: Oral

In Vitro Use Guide

Cells were treated with 25 and 50 mmol/L dichloroacetate for 24 hours, and cell-cycle profiles were analyzed using flow cytometry. Dichloroacetate treatment induced changes in the cell-cycle profiles of all tested glioblastoma cells. Specifically, after 24 hours of treatment with 25 mmol/L dichloroacetate, there was a slight increase (not significant) in the cells in G2–M phase in U87 and U251 cells and a 1.2-fold increase (P < 0.001) in RN1 cells. Significant increase in the mean percentage of all 3 tested cell lines in G2–M phase was observed when dichloroacetate dose was increased to 50 mmol/L. When compared with untreated control (U251, 8.8%; U87, 15.2%; RN1, 14.1%), dichloroacetate treatment increased the proportion of cells at G2–M phase to 35.5%, 34.7%, and 45.5%, respectively

Name

Type

Language

Sodium dichloroacetate

Official Name

English

SODIUM DICHLOROACETATE [MART.]

Common Name

English

SODIUM DICHLOROACETATE [USAN]

Common Name

English

CERESINE

Brand Name

English

CPC-211

Code

English

CMI X-11S

Code

English

NSC-744479

Code

English

DICHLOROACETATE SODIUM

Systematic Name

English

DCA SODIUM

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

114798