Identification

Name
Dihomo-gamma-linolenic acid
Accession Number
DB00154  (NUTR00032)
Type
Small Molecule
Groups
Approved, Investigational, Nutraceutical
Description

A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5. [PubChem]

Structure
Thumb
Synonyms
  • (8Z,11Z,14Z)-Icosatrienoic acid
  • (Z,Z,Z)-8,11,14-Eicosatrienoic acid
  • (Z,Z,Z)-8,11,14-Icosatrienoate
  • (Z,Z,Z)-8,11,14-Icosatrienoic acid
  • 20:3, n-6,9,12 all-cis
  • 8,11,14-Eicosatrienoic Acid
  • 8c,11c,14c-eicosatrienoic acid
  • 8c,11c,14c-Eicosatriensaeure
  • all-cis-8,11,14-eicosatrienoic acid
  • all-cis-8,11,14-icosatrienoic acid
  • all-cis-eicosa-8,11,14-trienoic acid
  • all-cis-Eicosa-8,11,14-triensaeure
  • all-cis-icosa-8,11,14-trienoic acid
  • C20:3, n-6,9,12 all-cis
  • cis,cis,cis-8,11,14-eicosatrienoic acid
  • DGLA
  • Dihomo-γ-linolenic acid
  • eicosa-8Z,11Z,14Z-trienoic acid
  • gamma-Homolinolenic acid
  • Homo-gamma-linolenic acid
  • Homo-gamma-linolensaeure
External IDs
20:3(N-6) / DS-107G / DS107G / RO 12-1989
International/Other Brands
Star GLA (GNC) / Tona-lean 1000 CLA (Action Labs)
Categories
UNII
FC398RK06S
CAS number
1783-84-2
Weight
Average: 306.4828
Monoisotopic: 306.255880332
Chemical Formula
C20H34O2
InChI Key
HOBAELRKJCKHQD-QNEBEIHSSA-N
InChI
InChI=1S/C20H34O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h6-7,9-10,12-13H,2-5,8,11,14-19H2,1H3,(H,21,22)/b7-6-,10-9-,13-12-
IUPAC Name
(8Z,11Z,14Z)-icosa-8,11,14-trienoic acid
SMILES
CCCCC\C=C/C\C=C/C\C=C/CCCCCCC(O)=O

Pharmacology

Indication

For nutritional supplementation, also for treating dietary shortage or imbalance

Structured Indications
Not Available
Pharmacodynamics

Dihomo gamma-linolenic acid or DHLA is an n-6 (omega-6) polyunsaturated fatty acid. It is comprised of 20 carbon atoms and three double bonds. DHLA is a byproduct of the 18 carbon gamma-linolenic acid (GLA). DHLA is then converted into prostaglandin E1 (PGE1). PGE1 inhibits platelet aggregation and also exerts a vasodilatory effect.

Mechanism of action

DHLA (or DGLA) is a precursor in the synthesis of prostaglandin E1 (PGE1) as well as the series-3 prostaglandins. It also serves as a precursor in the synthesis of eicosapentaenoic acid (EPA). EPA is a precursor of the series-3 prostaglandins, the series-5 leukotrienes and the series-3 thromboxanes. These eicosanoids have anti-thrombogenic, anti-inflammatory and anti-atherogenic properties. PGE1 inhibits platelet aggregation and has a vasodilation action. DHLA has also been shown to reduce the production/activity of tumor necrosis factor alpha.

TargetActionsOrganism
AProstaglandin G/H synthase 2Not AvailableHuman
AProstaglandin G/H synthase 1
inhibitor
Human
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
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Alpha Linolenic Acid and Linoleic Acid MetabolismMetabolic
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Hiroshi Kawashima, "Process for production of dihomo-gamma-linolenic acid and lipid containing same." U.S. Patent US20010021522, issued September 13, 2001.

US20010021522
General References
Not Available
External Links
Human Metabolome Database
HMDB02925
KEGG Compound
C03242
PubChem Compound
5280581
PubChem Substance
46508866
ChemSpider
4444199
BindingDB
50269534
ChEBI
53486
ChEMBL
CHEMBL465183
Therapeutic Targets Database
DAP000806
PharmGKB
PA164743249
HET
LAX
PDRhealth
PDRhealth Drug Page
PDB Entries
1fe2
MSDS
Download (71 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAtopic Dermatitis (AD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP6.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.71e-05 mg/mLALOGPS
logP7.24ALOGPS
logP6.95ChemAxon
logS-6.6ALOGPS
pKa (Strongest Acidic)4.89ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity98.84 m3·mol-1ChemAxon
Polarizability39.01 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9945
Blood Brain Barrier+0.9539
Caco-2 permeable+0.8371
P-glycoprotein substrateNon-substrate0.5962
P-glycoprotein inhibitor INon-inhibitor0.9487
P-glycoprotein inhibitor IINon-inhibitor0.8964
Renal organic cation transporterNon-inhibitor0.9272
CYP450 2C9 substrateNon-substrate0.7643
CYP450 2D6 substrateNon-substrate0.8954
CYP450 3A4 substrateNon-substrate0.6678
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.8972
CYP450 2D6 inhibitorNon-inhibitor0.9545
CYP450 2C19 inhibitorNon-inhibitor0.9467
CYP450 3A4 inhibitorNon-inhibitor0.9295
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9349
Ames testNon AMES toxic0.9674
CarcinogenicityNon-carcinogens0.6568
BiodegradationReady biodegradable0.811
Rat acute toxicity1.3991 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9133
hERG inhibition (predictor II)Non-inhibitor0.9103
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
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-0a4i-0019000000-38de24f5141b8fd24471
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-066v-9700000000-ea3e83fc76a5e8bf96a0
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-0k96-9200000000-2b1245d775cb6a9290a7
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
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-03di-0090000000-8151054828665541898d
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-05e9-0491000000-a09d13fe83820b375121
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-052e-0692000000-aba537ad7f934032649f
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as long-chain fatty acids. These are fatty acids with an aliphatic tail that contains between 13 and 21 carbon atoms.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty acids and conjugates
Direct Parent
Long-chain fatty acids
Alternative Parents
Unsaturated fatty acids / Straight chain fatty acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Long-chain fatty acid / Unsaturated fatty acid / Straight chain fatty acid / Monocarboxylic acid or derivatives / Carboxylic acid / Carboxylic acid derivative / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
long-chain fatty acid, icosatrienoic acid (CHEBI:53486) / Polyunsaturated fatty acids (C03242) / Unsaturated fatty acids (LMFA01030158)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Das UN: Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids? J Assoc Physicians India. 2005 Jul;53:623-7. [PubMed:16190133]
  2. Levin G, Duffin KL, Obukowicz MG, Hummert SL, Fujiwara H, Needleman P, Raz A: Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2. Biochem J. 2002 Jul 15;365(Pt 2):489-96. [PubMed:11939906]
  3. Das UN: COX-2 inhibitors and metabolism of essential fatty acids. Med Sci Monit. 2005 Jul;11(7):RA233-7. Epub 2005 Jun 29. [PubMed:15990700]
  4. Thuresson ED, Malkowski MG, Lakkides KM, Rieke CJ, Mulichak AM, Ginell SL, Garavito RM, Smith WL: Mutational and X-ray crystallographic analysis of the interaction of dihomo-gamma -linolenic acid with prostaglandin endoperoxide H synthases. J Biol Chem. 2001 Mar 30;276(13):10358-65. Epub 2000 Dec 19. [PubMed:11121413]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Levin G, Duffin KL, Obukowicz MG, Hummert SL, Fujiwara H, Needleman P, Raz A: Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2. Biochem J. 2002 Jul 15;365(Pt 2):489-96. [PubMed:11939906]
  2. Das UN: Can COX-2 inhibitor-induced increase in cardiovascular disease risk be modified by essential fatty acids? J Assoc Physicians India. 2005 Jul;53:623-7. [PubMed:16190133]
  3. Das UN: COX-2 inhibitors and metabolism of essential fatty acids. Med Sci Monit. 2005 Jul;11(7):RA233-7. Epub 2005 Jun 29. [PubMed:15990700]
  4. Thuresson ED, Malkowski MG, Lakkides KM, Rieke CJ, Mulichak AM, Ginell SL, Garavito RM, Smith WL: Mutational and X-ray crystallographic analysis of the interaction of dihomo-gamma -linolenic acid with prostaglandin endoperoxide H synthases. J Biol Chem. 2001 Mar 30;276(13):10358-65. Epub 2000 Dec 19. [PubMed:11121413]
  5. Malkowski MG, Thuresson ED, Lakkides KM, Rieke CJ, Micielli R, Smith WL, Garavito RM: Structure of eicosapentaenoic and linoleic acids in the cyclooxygenase site of prostaglandin endoperoxide H synthase-1. J Biol Chem. 2001 Oct 5;276(40):37547-55. Epub 2001 Jul 27. [PubMed:11477109]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transporter activity
Specific Function
B-FABP could be involved in the transport of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development. It is required for the establishment of the radial glial...
Gene Name
FABP7
Uniprot ID
O15540
Uniprot Name
Fatty acid-binding protein, brain
Molecular Weight
14888.855 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:34