DIISOPROPYLAMMONIUM DICHLOROACETATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H15N.C2H2Cl2O2
Molecular Weight	230.132
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of DIISOPROPYLAMMONIUM DICHLOROACETATE

Structure Search

SMILES

OC(=O)C(Cl)Cl.CC(C)NC(C)C

InChI

InChIKey=ILKBHIBYKSHTKQ-UHFFFAOYSA-N

InChI=1S/C6H15N.C2H2Cl2O2/c1-5(2)7-6(3)4;3-1(4)2(5)6/h5-7H,1-4H3;1H,(H,5,6)

HIDE SMILES / InChI

Molecular Formula	C6H15N
Molecular Weight	101.19
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C2H2Cl2O2
Molecular Weight	128.942
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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(dichloroacetate), is an acid analog of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms.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
trans-Activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals.	1999 Dec 1	10581215
Effect of trichloroethylene and its metabolites, dichloroacetic acid and trichloroacetic acid, on the methylation and expression of c-Jun and c-Myc protooncogenes in mouse liver: prevention by methionine.	2000 Apr	10774822
Gene transfer and metabolic modulators as new therapies for pulmonary hypertension. Increasing expression and activity of potassium channels in rat and human models.	2001	11950153
[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
Direct imaging of dehydrogenase activity within living cells using enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP).	2001 Apr	11259315
Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak.	2001 Apr	11247790
Haloacetates in fog and rain.	2001 Apr 1	11348059
Detection of early gene expression changes by differential display in the livers of mice exposed to dichloroacetic acid.	2001 Aug	11470764
Trichloroethylene oxidative metabolism in plants: the trichloroethanol pathway.	2001 Dec	11730869
Diffusion-weighted image and MR spectroscopic analysis of a case of MELAS with repeated attacks.	2001 Feb	11293491
Lactic acidosis update for critical care clinicians.	2001 Feb	11251027
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
Lack of IL-6 production during exercise in patients with mitochondrial myopathy.	2001 Jan-Feb	11394246
Nerve conduction changes in patients with mitochondrial diseases treated with dichloroacetate.	2001 Jul	11410919
Study on the cytochrome P-450- and glutathione-dependent biotransformation of trichloroethylene in humans.	2001 Mar	11317702
Differential effects of dihalogenated and trihalogenated acetates in the liver of B6C3F1 mice.	2001 Mar-Apr	11288130
GSTZ1d: a new allele of glutathione transferase zeta and maleylacetoacetate isomerase.	2001 Nov	11692075
Trichloroethylene, trichloroacetic acid, and dichloroacetic acid: do they affect fetal rat heart development?	2001 Sep-Oct	11766123
Genetic polymorphisms in assessing interindividual variability in delivered dose.	2002 Apr	12052003
[Drug therapy for mitochondrial diseases].	2002 Apr	12013970
Low-dose pharmacokinetics and oral bioavailability of dichloroacetate in naive and GST-zeta-depleted rats.	2002 Aug	12153755
Dichloroacetate stimulates glycogen accumulation in primary hepatocytes through an insulin-independent mechanism.	2002 Aug	12151648
Monochloramine loss in the presence of humic acid.	2002 Feb	11871712
Enhanced pyruvate dehydrogenase activity does not affect muscle O2 uptake at onset of intense exercise in humans.	2002 Jan	11742848
Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channels.	2002 Jan 15	11790708
Skeletal muscle metabolism is unaffected by DCA infusion and hyperoxia after onset of intense aerobic exercise.	2002 Jul	12067850
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
Brief increase in carbohydrate oxidation after reperfusion reverses myocardial stunning in conscious pigs.	2002 Nov 26	12451011
[Acute complications due to diabetes mellitus: Lactic acidosis].	2002 Oct	12430218
Chloroacetic acids in European soils and vegetation.	2003 Apr	12729268
Measurement of 13C/12C of chloroacetic acids by gas chromatography/combustion/isotope ratio mass spectrometry.	2003 Feb	12504128
Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart.	2003 Jul	12793977
Perturbation of maleylacetoacetic acid metabolism in rats with dichloroacetic Acid-induced glutathione transferase zeta deficiency.	2003 Jul	12730618
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

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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:16:20 GMT 2023` Edited by `admin` on `Fri Dec 15 15:16:20 GMT 2023`
Record UNII	BA6QDP0R4E
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DIISOPROPYLAMMONIUM DICHLOROACETATE

Systematic Name

English

OXYPANGAM

Brand Name

English

2,2-DICHLOROACETIC ACID COMPD WITH N-(1-METHYLETHYL)-2-PROPANAMINE (1:1)

Common Name

English

DICHLOROACETIC ACID DIISOPROPYLAMMONIUM SALT

Common Name

English

DI-ISOPROPYLAMMONIUM DICHLOROACETATE [MART.]

Common Name

English

DI-ISOPROPYLAMINE DICHLOROACETATE

Systematic Name

English

DISOTAT

Brand Name

English

DIISOPROPYLAMINE DICHLOROACETATE

Systematic Name

English

DIISOPROPYLAMINE DICHLOROACETATE [JAN]

Common Name

English

IS-401

Code

English

DIPA-DCA

Common Name

English

Diisopropylamine dichloroacetate [WHO-DD]

Common Name

English

DIISOPROPYLAMINE DICHLOROACETATE [MI]

Common Name

English

KALODIL

Brand Name

English

Code System Code Type Description

FDA UNII

BA6QDP0R4E