Dichloroacetic Acid

Identification

Name
Dichloroacetic Acid
Accession Number
DB08809
Type
Small Molecule
Groups
Experimental
Description

Dichloroacetic acid, often abbreviated DCA, is an acid analogue of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms.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.

Structure
Thumb
Synonyms
  • DCA
  • dichloracetic acid
  • dichloroacetate
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bichloracetic Acid 100%Liquid100 %TopicalGlenwood Inc.1989-12-312010-07-16Canada
Categories
UNII
9LSH52S3LQ
CAS number
79-43-6
Weight
Average: 128.942
Monoisotopic: 127.943184722
Chemical Formula
C2H2Cl2O2
InChI Key
JXTHNDFMNIQAHM-UHFFFAOYSA-N
InChI
InChI=1S/C2H2Cl2O2/c3-1(4)2(5)6/h1H,(H,5,6)
IUPAC Name
2,2-dichloroacetic acid
SMILES
OC(=O)C(Cl)Cl

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
A[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial
inhibitor
Human
UMaleylacetoacetate isomeraseNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

ORAL (LD50): Acute: 2820 mg/kg [Rat]; DERMAL (LD50): Acute: 510 mg/kg [Rabbit]

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Joanne D. Burger, William L. Howard, "Method for preparing pentachloroacetone and dichloroacetic acid from isopropyl ethers." U.S. Patent US3996272, issued August, 1968.

US3996272
General References
Not Available
External Links
KEGG Compound
C11149
PubChem Compound
6597
PubChem Substance
175427097
ChemSpider
10771217
ChEBI
36386
ChEMBL
CHEMBL13960
PharmGKB
PA165947835
HET
TF4
Wikipedia
Dichloroacetic_acid
PDB Entries
2bu8 / 2q8h
MSDS
Download (49.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingScreeningHealthy Volunteers1
1CompletedHealth Services ResearchHealthy Volunteers1
1CompletedTreatmentGlioblastomas / Neoplasms, Brain1
1CompletedTreatmentHead and Neck Carcinoma1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentPulmonary Hypertension (Idiopathic, Familial or Anorexigen-associated)1
1WithdrawnTreatmentGlioblastomas1
1, 2CompletedBasic ScienceHealthy Volunteers1
2Active Not RecruitingTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
2CompletedTreatmentMalignant Gliomas, Glioblastoma Multiforme1
2TerminatedTreatmentLung Cancers / Metastatic Breast Cancer (MBC)1
2Unknown StatusTreatmentMELAS Syndrome1
3RecruitingTreatmentPyruvate Dehydrogenase Complex Deficiency1
4Active Not RecruitingBasic ScienceInsulin Resistance1
Not AvailableCompletedNot AvailableCongenital Lactic Acidosis1
Not AvailableCompletedPreventionAcidosis, Respiratory / Chronic Diseases1
Not AvailableCompletedScreeningAcidosis, Respiratory1
Not AvailableNo Longer AvailableNot AvailableMitochondrial Enzyme Deficiencies1
Not AvailableTerminatedBasic ScienceHealthy Volunteers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidTopical100 %
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)13.5 °CPhysProp
boiling point (°C)194 °CPhysProp
water solubility1E+006 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.92HANSCH,C ET AL. (1995)
pKa1.26MARUTHAMUTHU,P & HUIE,RE (1995)
Predicted Properties
PropertyValueSource
Water Solubility72.3 mg/mLALOGPS
logP0.99ALOGPS
logP1.06ChemAxon
logS-0.25ALOGPS
pKa (Strongest Acidic)2.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity22.62 m3·mol-1ChemAxon
Polarizability9.32 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9891
Blood Brain Barrier+0.9763
Caco-2 permeable+0.6135
P-glycoprotein substrateNon-substrate0.9118
P-glycoprotein inhibitor INon-inhibitor0.9924
P-glycoprotein inhibitor IINon-inhibitor0.9909
Renal organic cation transporterNon-inhibitor0.9443
CYP450 2C9 substrateNon-substrate0.7947
CYP450 2D6 substrateNon-substrate0.9283
CYP450 3A4 substrateNon-substrate0.7764
CYP450 1A2 substrateNon-inhibitor0.7252
CYP450 2C9 inhibitorNon-inhibitor0.8954
CYP450 2D6 inhibitorNon-inhibitor0.9359
CYP450 2C19 inhibitorNon-inhibitor0.9162
CYP450 3A4 inhibitorNon-inhibitor0.9544
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9909
Ames testAMES toxic0.5797
CarcinogenicityCarcinogens 0.7098
BiodegradationReady biodegradable0.5292
Rat acute toxicity1.9655 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9854
hERG inhibition (predictor II)Non-inhibitor0.9796
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Mass Spectrum (Electron Ionization)MSsplash10-0002-9000000000-5cc2c87638085fad9afc
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0059-6900000000-9d33b2f109bd8208b818
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-9000000000-cdde3faa793ecb51af1b
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-9000000000-c1ded91474fde2787d95
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0019-9000000000-cea4fe3c3f1653aa150d
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-9000000000-68d75216c4534c61a4b4
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0059-6900000000-55338ed4fe8335b6f8ba
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-9000000000-d0c2081f59cf4a1d9bb9
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-9000000000-aa8cfce9c157e8ce5c26
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0019-9000000000-d0fd266005ba1e11af9f
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-9000000000-67e8e2a12579c484a9d1
1H NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha-halocarboxylic acids. These are carboxylic acids containing a halogen atom bonded to the alpha carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Alpha-halocarboxylic acids and derivatives
Direct Parent
Alpha-halocarboxylic acids
Alternative Parents
Monocarboxylic acids and derivatives / Carboxylic acids / Organochlorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Alkyl chlorides
Substituents
Alpha-halocarboxylic acid / Monocarboxylic acid or derivatives / Carboxylic acid / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Organochloride / Organohalogen compound / Carbonyl group
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
monocarboxylic acid, organochlorine compound (CHEBI:36386) / Halogenated fatty acids (LMFA01090070)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Pyruvate dehydrogenase (acetyl-transferring) kinase activity
Specific Function
Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate de...
Gene Name
PDK1
Uniprot ID
Q15118
Uniprot Name
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial
Molecular Weight
49243.765 Da
References
  1. Stacpoole PW: The pharmacology of dichloroacetate. Metabolism. 1989 Nov;38(11):1124-44. [PubMed:2554095]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Bifunctional enzyme showing minimal glutathione-conjugating activity with ethacrynic acid and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole and maleylacetoacetate isomerase activity. Has also low glutathi...
Gene Name
GSTZ1
Uniprot ID
O43708
Uniprot Name
Maleylacetoacetate isomerase
Molecular Weight
24212.005 Da
References
  1. Anderson WB, Liebler DC, Board PG, Anders MW: Mass spectral characterization of dichloroacetic acid-modified human glutathione transferase zeta. Chem Res Toxicol. 2002 Nov;15(11):1387-97. [PubMed:12437329]

Drug created on January 06, 2011 16:41 / Updated on October 02, 2017 06:10