Identification

Name
Doconexent
Accession Number
DB03756  (EXPT01798, DB11070)
Type
Small Molecule
Groups
Approved, Investigational
Description

A mixture of fish oil and primrose oil, doconexent is used as a high-docosahexaenoic acid (DHA) supplement. DHA is a 22 carbon chain with 6 cis double bonds with anti-inflammatory effects. It can be biosythesized from alpha-linolenic acid or commercially manufactured from microalgae. It is an omega-3 fatty acid and primary structural component of the human brain, cerebral cortex, skin, and retina thus plays an important role in their development and function. The amino-phospholipid DHA is found at a high concentration across several brain subcellular fractions, including nerve terminals, microsomes, synaptic vesicles, and synaptosomal plasma membranes [10].

Structure
Thumb
Synonyms
  • (4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid
  • 22:6-4, 7,10,13,16,19
  • 22:6(n-3)
  • 4,7,10,13,16,19-docosahexaenoic acid
  • 4,7,10,13,16,19-Docosahexaenoic acid
  • all-cis-4,7,10,13,16,19-docosahexaenoic acid
  • all-cis-DHA
  • cervonic acid
  • DHA
  • docosa-4,7,10,13,16,19-hexaenoic acid
  • Docosahexaenoic acid
Product Ingredients
IngredientUNIICASInChI Key
Doconexent sodium295P7EPT4C81926-93-4SNNDEWVSGZRIFE-FPYKSTABSA-M
Product Images
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Natelle OneDoconexent (250 mg/1) + Ascorbic acid (30 mg/1) + Calcium phosphate, tribasic (100 mg/1) + Ferrous fumarate (27 mg/1) + Folic Acid (1 mg/1) + Icosapent (.625 mg/1) + Pyridoxine hydrochloride (25 mg/1) + Vitamin E (30 [iU]/1)Capsule, gelatin coatedOralAzur Pharma, Inc.2009-11-09Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Animi-3Doconexent (250 mg/1) + Cholecalciferol (1000 [iU]/1) + Cyanocobalamin (500 ug/1) + Folic Acid (1 mg/1) + Icosapent (35 mg/1) + Omega-3 fatty acids (500 mg/1) + Pyridoxine hydrochloride (12.5 mg/1) + Soy sterol (200 mg/1)CapsuleOralPbm Pharmaceuticals Inc.2011-06-01Not applicableUs
Animi-3 with Vitamin DDoconexent (250 mg/1) + Cholecalciferol (1000 [iU]/1) + Cyanocobalamin (500 ug/1) + Folic Acid (1 mg/1) + Icosapent (35 mg/1) + Omega-3 fatty acids (500 mg/1) + Pyridoxine hydrochloride (12.5 mg/1) + Soy sterol (200 mg/1)CapsuleOralPbm Pharmaceuticals Inc.2011-06-01Not applicableUs
CitraNatal AssureDoconexent + IcosapentKitMission Pharmacal2014-04-30Not applicableUs
CitraNatal Bloom DHADoconexent + Docusate sodiumKitOralMission Pharmacal2018-01-18Not applicableUs
CitraNatal HarmonyDoconexent (250 mg/1) + Calcium Citrate (100 mg/1) + Cholecalciferol (400 [iU]/1) + DL-alpha-Tocopherol (30 [iU]/1) + Docusate sodium (50 mg/1) + Folic Acid (1 mg/1) + Iron (27 mg/1) + Pyridoxine hydrochloride (25 mg/1)Capsule, gelatin coatedOralMission Pharmacal2010-04-27Not applicableUs
CitraNatal HarmonyDoconexent (250 mg/1) + Calcium Citrate (100 mg/1) + Cholecalciferol (400 [iU]/1) + DL-alpha-Tocopherol (30 [iU]/1) + Docusate sodium (50 mg/1) + Folic Acid (1 mg/1) + Iron (28 mg/1) + Pyridoxine hydrochloride (25 mg/1)Capsule, gelatin coatedOralMission Pharmacal2011-04-18Not applicableUs
CitraNatal HarmonyDoconexent (260 mg/1) + Calcium Citrate (104 mg/1) + Cholecalciferol (400 [iU]/1) + DL-alpha-Tocopherol (30 [iU]/1) + Docusate sodium (50 mg/1) + Folic Acid (1 mg/1) + Iron (30 mg/1) + Pyridoxine hydrochloride (25 mg/1)Capsule, gelatin coatedOralMission Pharmacal2012-01-15Not applicableUs
CitraNatal Harmony 3.0Doconexent (260 mg/1) + Calcium Citrate (104 mg/1) + Cholecalciferol (400 [iU]/1) + Docusate sodium (50 mg/1) + Folic Acid (1 mg/1) + Iron (27 mg/1) + Pyridoxine (25 mg/1) + Vitamin E (30 [iU]/1)Capsule, gelatin coatedOralMission Pharmacal2014-03-21Not applicableUs
CitraNatal MedleyDoconexent (200 mg/1) + Calcium Citrate (62 mg/1) + Cholecalciferol (200 [iU]/1) + Ferrous fumarate (2 mg/1) + Folic Acid (1 mg/1) + Iron (27 mg/1) + Pyridoxine (12.5 mg/1) + Vitamin E (15 [iU]/1)Capsule, gelatin coatedOralMission Pharmacal2018-03-20Not applicableUs
Extra-Virt Plus DHADoconexent (350 mg/1) + Ascorbic acid (28 mg/1) + Biotin (250 ug/1) + Calcium Carbonate (158 mg/1) + Cholecalciferol (800 [iU]/1) + Docusate calcium (55 mg/1) + Ferrous fumarate (29 mg/1) + Folic Acid (1.25 mg/1) + Pyridoxine hydrochloride (25 mg/1) + Vitamin E (30 [iU]/1)Capsule, gelatin coatedOralVirtus Pharmaceuticals2012-12-28Not applicableUs
Categories
UNII
ZAD9OKH9JC
CAS number
6217-54-5
Weight
Average: 328.4883
Monoisotopic: 328.240230268
Chemical Formula
C22H32O2
InChI Key
MBMBGCFOFBJSGT-KUBAVDMBSA-N
InChI
InChI=1S/C22H32O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24/h3-4,6-7,9-10,12-13,15-16,18-19H,2,5,8,11,14,17,20-21H2,1H3,(H,23,24)/b4-3-,7-6-,10-9-,13-12-,16-15-,19-18-
IUPAC Name
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid
SMILES
CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O

Pharmacology

Indication

Used as a high-docosahexaenoic acid (DHA) oral supplement.

Associated Therapies
Pharmacodynamics

DHA in the central nervous system is found in the phospholipid bilayers where it modulates the physical environment and increase the free volume within the membrane bilayer. It influences the G-protein coupled receptor activity and affects transmembrane transport and cell interaction with the exterior world. It is also reported to promote apoptosis, neuronal differentiation and ion channel activity. Like other polyunsaturated fatty acids, DHA acts as a ligand at PPARs that plays an anti-inflammatory effect and regulate inflammatory gene expression and NFκB activation. DHA also gives rise to resolvins and related compounds (e.g., protectins) through pathways involving cyclooxygenase and lipoxygenase enzymes to resolve the inflammatory responses.

Mechanism of action

DHA and its conversion to other lipid signalling moleccules compete with the arachidonic acid cascade from endogenous phospholipids and shift the inflammatory state to being more anti-inflammatory. DHA inhibits endotoxin-stimulated production of IL-6 and IL-8 in human endothelial cells. Derivatives of DHA are anti-inflammatory lipid mediators. Lipid mediators resolvin D1 and protectin D1 all inhibit transendothelial migration of neutrophils, so preventing neutrophilic infiltration at sites of inflammation, resolvin D1 inhibits IL-1β production, and protectin D1 inhibits TNF and IL-1β production [1]. Monoxydroxy derivative of DHA converted by LOX inhibit thromboxane-induced platelet aggregation. DHA supplementation has also shown to reduce the levels of serum C-reactive protein (CRP) and other circulating markers of inflammation such as neutrophils in hypertriglyceridemic men [12]. DHA acts as a ligand at peroxisome proliferator-activated receptor (PPAR) gamma and alpha that regulate lipid signalling molecule-mediated transduction pathways and modulate inflammation. As a natural ligand, DHA induces a protective effect in retinal tissues by activating retinoid x receptors and subsequent ERK/MAPK signaling pathway in photoreceptors to promote their survival and differentiation, stimulating the expression of antiapoptotic proteins such as Bcl-2 and preserving mitochondrial membrane potential [A19453].

TargetActionsOrganism
APeroxisome proliferator-activated receptor alpha
ligand
Human
APeroxisome proliferator-activated receptor gamma
ligand
Human
ARetinoic acid receptor RXR-alpha
activator
Human
ARetinoic acid receptor RXR-beta
activator
Human
ARetinoic acid receptor RXR-gamma
activator
Human
USterol regulatory element-binding protein 1
inhibitor
Human
Absorption

Like other omega-3 fatty acids, DHA is hydrolyzed from the intestines and delivered through the lymphatic circulation. Plasma DHA concentrations increase in a dose-dependent and saturable manner.

Volume of distribution

DHA is the most abundant n−3 fatty acid in membranes and is present in all organs. It is also the most variable among organs and is particularly abundant in neural tissue, such as brain and retina, where it is several hundred-fold more abundant than EPA [13].

Protein binding
Not Available
Metabolism

DHA can be metabolized into DHA-derived specialized pro-resolving mediators (SPMs), DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids, among others. It is converted to 17-hydroperoxy-DHA derivatives via COX-2 and 15-LOX and 5-LOX activity. These derivatives are further converted into D-series resolvins and protectins with potent anti-inflammatory potential and potent neuroprotective effect [3]. DHA may also be metabolized to 19,20-epoxydocosapentaenoic acids (EDPs) and isomers via CYP2C9 activity. Epoxy metabolites are reported to mediate anti-tumor activity by inhibiting angiogenesis, tumor growth, and metastasis.

Route of elimination
Not Available
Half life

Approximately 20 hours [9].

Clearance
Not Available
Toxicity

Oral LD50 value in rats is 7,060 mg/kg and 3,450 mg/kg in mouse. Adverse effects include anemia, cough, CNS depression, drowsiness, headache, heart damage, lassitude (weakness, exhaustion), liver damage, narcosis, reproductive effects and teratogenic effects.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe metabolism of Doconexent can be decreased when combined with Abiraterone.Approved
Acetyl sulfisoxazoleThe metabolism of Doconexent can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AmiodaroneThe metabolism of Doconexent can be decreased when combined with Amiodarone.Approved, Investigational
ApalutamideThe serum concentration of Doconexent can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe metabolism of Doconexent can be increased when combined with Aprepitant.Approved, Investigational
CapecitabineThe metabolism of Doconexent can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Doconexent can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Doconexent can be increased when it is combined with Ceritinib.Approved
CholecalciferolThe metabolism of Doconexent can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
ClotrimazoleThe metabolism of Doconexent can be decreased when combined with Clotrimazole.Approved, Vet Approved
CrisaboroleThe metabolism of Doconexent can be decreased when combined with Crisaborole.Approved, Investigational
CurcuminThe metabolism of Doconexent can be decreased when combined with Curcumin.Approved, Investigational
CyclosporineThe metabolism of Doconexent can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Doconexent can be decreased when it is combined with Dabrafenib.Approved, Investigational
DelavirdineThe metabolism of Doconexent can be decreased when combined with Delavirdine.Approved
DosulepinThe metabolism of Doconexent can be decreased when combined with Dosulepin.Approved
EfavirenzThe metabolism of Doconexent can be decreased when combined with Efavirenz.Approved, Investigational
EtravirineThe metabolism of Doconexent can be decreased when combined with Etravirine.Approved
FloxuridineThe metabolism of Doconexent can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Doconexent can be decreased when combined with Fluconazole.Approved, Investigational
FluorouracilThe metabolism of Doconexent can be decreased when combined with Fluorouracil.Approved
FluvastatinThe metabolism of Doconexent can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Doconexent can be decreased when combined with Fluvoxamine.Approved, Investigational
FosphenytoinThe metabolism of Doconexent can be increased when combined with Fosphenytoin.Approved, Investigational
GemfibrozilThe metabolism of Doconexent can be decreased when combined with Gemfibrozil.Approved
IndinavirThe metabolism of Doconexent can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Doconexent can be decreased when combined with Irbesartan.Approved, Investigational
KetoconazoleThe metabolism of Doconexent can be decreased when combined with Ketoconazole.Approved, Investigational
LeflunomideThe metabolism of Doconexent can be decreased when combined with Leflunomide.Approved, Investigational
LobeglitazoneThe metabolism of Doconexent can be decreased when combined with Lobeglitazone.Approved, Investigational
LosartanThe metabolism of Doconexent can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Doconexent can be decreased when combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Doconexent can be decreased when it is combined with Lumacaftor.Approved
ManidipineThe metabolism of Doconexent can be decreased when combined with Manidipine.Approved, Investigational
MidostaurinThe metabolism of Doconexent can be decreased when combined with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Doconexent can be increased when it is combined with Mifepristone.Approved, Investigational
NabiloneThe metabolism of Doconexent can be decreased when combined with Nabilone.Approved, Investigational
NicardipineThe metabolism of Doconexent can be decreased when combined with Nicardipine.Approved, Investigational
OmeprazoleThe metabolism of Doconexent can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of Doconexent can be increased when combined with Phenobarbital.Approved, Investigational
PhenytoinThe metabolism of Doconexent can be increased when combined with Phenytoin.Approved, Vet Approved
PrimidoneThe metabolism of Doconexent can be increased when combined with Primidone.Approved, Vet Approved
PyrimethamineThe metabolism of Doconexent can be decreased when combined with Pyrimethamine.Approved, Investigational, Vet Approved
QuinineThe metabolism of Doconexent can be decreased when combined with Quinine.Approved
RifampicinThe metabolism of Doconexent can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Doconexent can be increased when combined with Rifapentine.Approved, Investigational
RucaparibThe metabolism of Doconexent can be decreased when combined with Rucaparib.Approved, Investigational
SecobarbitalThe metabolism of Doconexent can be increased when combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Doconexent can be decreased when combined with Sildenafil.Approved, Investigational
SorafenibThe metabolism of Doconexent can be decreased when combined with Sorafenib.Approved, Investigational
SulfadiazineThe metabolism of Doconexent can be decreased when combined with Sulfadiazine.Approved, Investigational, Vet Approved
SulfamethoxazoleThe metabolism of Doconexent can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Doconexent can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TicagrelorThe metabolism of Doconexent can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Doconexent can be decreased when combined with Ticlopidine.Approved
TolbutamideThe metabolism of Doconexent can be decreased when combined with Tolbutamide.Approved, Investigational
TopiroxostatThe metabolism of Doconexent can be decreased when combined with Topiroxostat.Approved, Investigational
TrimethoprimThe metabolism of Doconexent can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Doconexent can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Doconexent can be decreased when combined with Valsartan.Approved, Investigational
VoriconazoleThe metabolism of Doconexent can be decreased when combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Doconexent can be decreased when combined with Zafirlukast.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Calder PC: Omega-3 fatty acids and inflammatory processes. Nutrients. 2010 Mar;2(3):355-74. doi: 10.3390/nu2030355. Epub 2010 Mar 18. [PubMed:22254027]
  2. Kim HY: Novel metabolism of docosahexaenoic acid in neural cells. J Biol Chem. 2007 Jun 29;282(26):18661-5. Epub 2007 May 8. [PubMed:17488715]
  3. Picq M, Chen P, Perez M, Michaud M, Vericel E, Guichardant M, Lagarde M: DHA metabolism: targeting the brain and lipoxygenation. Mol Neurobiol. 2010 Aug;42(1):48-51. doi: 10.1007/s12035-010-8131-7. Epub 2010 Apr 28. [PubMed:20422316]
  4. Butovich IA, Lukyanova SM, Bachmann C: Dihydroxydocosahexaenoic acids of the neuroprotectin D family: synthesis, structure, and inhibition of human 5-lipoxygenase. J Lipid Res. 2006 Nov;47(11):2462-74. Epub 2006 Aug 9. [PubMed:16899822]
  5. Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA: Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol. 2006 Feb 1;176(3):1848-59. [PubMed:16424216]
  6. Mas E, Croft KD, Zahra P, Barden A, Mori TA: Resolvins D1, D2, and other mediators of self-limited resolution of inflammation in human blood following n-3 fatty acid supplementation. Clin Chem. 2012 Oct;58(10):1476-84. Epub 2012 Aug 21. [PubMed:22912397]
  7. Chen CT, Kitson AP, Hopperton KE, Domenichiello AF, Trepanier MO, Lin LE, Ermini L, Post M, Thies F, Bazinet RP: Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain. Sci Rep. 2015 Oct 29;5:15791. doi: 10.1038/srep15791. [PubMed:26511533]
  8. Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N Jr: Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res. 2001 Aug;42(8):1257-65. [PubMed:11483627]
  9. Pawlosky RJ, Hibbeln JR, Salem N Jr: Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers. J Lipid Res. 2007 Apr;48(4):935-43. Epub 2007 Jan 17. [PubMed:17234605]
  10. Cederholm T, Salem N Jr, Palmblad J: omega-3 fatty acids in the prevention of cognitive decline in humans. Adv Nutr. 2013 Nov 6;4(6):672-6. doi: 10.3945/an.113.004556. eCollection 2013 Nov. [PubMed:24228198]
  11. Guesnet P, Alessandri JM: Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations. Biochimie. 2011 Jan;93(1):7-12. doi: 10.1016/j.biochi.2010.05.005. Epub 2010 May 15. [PubMed:20478353]
  12. Kelley DS, Siegel D, Fedor DM, Adkins Y, Mackey BE: DHA supplementation decreases serum C-reactive protein and other markers of inflammation in hypertriglyceridemic men. J Nutr. 2009 Mar;139(3):495-501. doi: 10.3945/jn.108.100354. Epub 2009 Jan 21. [PubMed:19158225]
  13. Arterburn LM, Hall EB, Oken H: Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1467S-1476S. [PubMed:16841856]
External Links
Human Metabolome Database
HMDB0002183
KEGG Compound
C06429
PubChem Compound
445580
PubChem Substance
46506213
ChemSpider
393183
BindingDB
50210259
ChEBI
28125
ChEMBL
CHEMBL367149
HET
HXA
Wikipedia
Docosahexaenoic_acid
PDB Entries
1fdq / 1mv9 / 2byo / 2g7z / 2vv0 / 3hs7 / 5j0z
MSDS
Download (28.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentConcussions / Mild Traumatic Brain Injury (MTBI)1
1CompletedTreatmentColitis / Primary Sclerosing Cholangitis (PSC)1
1CompletedTreatmentHealthy Volunteers1
1, 2CompletedTreatmentBMI >30 kg/m2 / Fatty Liver / Fibrosis, Liver / Metabolic Syndromes / Nonalcoholic Fatty Liver Disease1
1, 2Not Yet RecruitingTreatmentAmblyopia1
2Active Not RecruitingPreventionBenign Breast Neoplasm / Ductal Breast Carcinoma In Situ / Invasive Breast Carcinoma / Lobular Breast Carcinoma In Situ / Paget Disease of the Breast / Stage IA Breast Cancer / Stage IB Breast Cancer / Stage IIA Breast Cancer / Stage IIB Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer1
2Active Not RecruitingTreatmentSickle Cell Disorders1
2CompletedTreatmentCystic Fibrosis (CF)1
3CompletedTreatmentAlzheimer's Disease (AD)1
3Not Yet RecruitingTreatmentSickle Cell Disorders1
4Active Not RecruitingTreatmentChild's Development / Premature Births1
4CompletedOtherBioavailability1
4CompletedPreventionPlasmodium Infections1
Not AvailableCompletedTreatmentCoronary Artery Disease / Coronary Risk Equivalent / Diabetes Mellitus (DM) / Hyperlipidemias / Hypertriglyceridemia (TG>200<500)1
Not AvailableCompletedTreatmentRetinitis Pigmentosa (RP)1
Not AvailableWithdrawnTreatmentHypertension in Pregnancy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral
KitOral
Tablet, film coatedOral
Capsule, liquid filledOral
Kit
Tablet, coatedOral
TabletOral
Capsule, gelatin coatedOral
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000186 mg/mLALOGPS
logP6.83ALOGPS
logP6.75ChemAxon
logS-6.2ALOGPS
pKa (Strongest Acidic)4.89ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity111.39 m3·mol-1ChemAxon
Polarizability38.63 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9944
Blood Brain Barrier+0.9277
Caco-2 permeable+0.7696
P-glycoprotein substrateNon-substrate0.7069
P-glycoprotein inhibitor INon-inhibitor0.9369
P-glycoprotein inhibitor IINon-inhibitor0.9152
Renal organic cation transporterNon-inhibitor0.9399
CYP450 2C9 substrateNon-substrate0.8035
CYP450 2D6 substrateNon-substrate0.9101
CYP450 3A4 substrateNon-substrate0.7197
CYP450 1A2 substrateInhibitor0.6216
CYP450 2C9 inhibitorNon-inhibitor0.9094
CYP450 2D6 inhibitorNon-inhibitor0.964
CYP450 2C19 inhibitorNon-inhibitor0.9717
CYP450 3A4 inhibitorNon-inhibitor0.944
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9588
Ames testNon AMES toxic0.8998
CarcinogenicityNon-carcinogens0.627
BiodegradationReady biodegradable0.8443
Rat acute toxicity1.4856 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.873
hERG inhibition (predictor II)Non-inhibitor0.9343
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
GC-MS Spectrum - GC-MS (1 TMS)GC-MSsplash10-004l-9800000000-86f34228f9e92b6da2c6
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-MSGC-MSsplash10-004l-9800000000-86f34228f9e92b6da2c6
Mass Spectrum (Electron Ionization)MSsplash10-002f-9400000000-60bd7bfd4de9015476c7
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-IT , negativeLC-MS/MSsplash10-001i-0190000000-e6566b5aff7cefa4ae5d
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-0069000000-c76c91e0abd1895adb8b
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001r-0069000000-a25e6a700612620a1217

Taxonomy

Description
This compound belongs to the class of organic compounds known as very long-chain fatty acids. These are fatty acids with an aliphatic tail that contains at least 22 carbon atoms.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty acids and conjugates
Direct Parent
Very 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
Very 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
omega-3 fatty acid, docosahexaenoic acid (CHEBI:28125) / Unsaturated fatty acids, Docosanoids, Polyunsaturated fatty acids (C06429) / Unsaturated fatty acids (LMFA01030185)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Ligand
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Liu M, Montgomery MK, Fiveash CE, Osborne B, Cooney GJ, Bell-Anderson K, Turner N: PPARalpha-independent actions of omega-3 PUFAs contribute to their beneficial effects on adiposity and glucose homeostasis. Sci Rep. 2014 Jul 2;4:5538. doi: 10.1038/srep05538. [PubMed:24986106]
  2. Rudkowska I, Garenc C, Couture P, Vohl MC: Omega-3 fatty acids regulate gene expression levels differently in subjects carrying the PPARalpha L162V polymorphism. Genes Nutr. 2009 Sep;4(3):199-205. doi: 10.1007/s12263-009-0129-2. Epub 2009 Jul 8. [PubMed:19585164]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Ligand
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Varga T, Czimmerer Z, Nagy L: PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochim Biophys Acta. 2011 Aug;1812(8):1007-22. doi: 10.1016/j.bbadis.2011.02.014. Epub 2011 Mar 5. [PubMed:21382489]
  2. Edwards IJ, O'Flaherty JT: Omega-3 Fatty Acids and PPARgamma in Cancer. PPAR Res. 2008;2008:358052. doi: 10.1155/2008/358052. [PubMed:18769551]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Activator
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRA
Uniprot ID
P19793
Uniprot Name
Retinoic acid receptor RXR-alpha
Molecular Weight
50810.835 Da
References
  1. German OL, Monaco S, Agnolazza DL, Rotstein NP, Politi LE: Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors. J Lipid Res. 2013 Aug;54(8):2236-46. doi: 10.1194/jlr.M039040. Epub 2013 May 30. [PubMed:23723389]
  2. de Urquiza AM, Liu S, Sjoberg M, Zetterstrom RH, Griffiths W, Sjovall J, Perlmann T: Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science. 2000 Dec 15;290(5499):2140-4. [PubMed:11118147]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Activator
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRB
Uniprot ID
P28702
Uniprot Name
Retinoic acid receptor RXR-beta
Molecular Weight
56921.38 Da
References
  1. German OL, Monaco S, Agnolazza DL, Rotstein NP, Politi LE: Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors. J Lipid Res. 2013 Aug;54(8):2236-46. doi: 10.1194/jlr.M039040. Epub 2013 May 30. [PubMed:23723389]
  2. de Urquiza AM, Liu S, Sjoberg M, Zetterstrom RH, Griffiths W, Sjovall J, Perlmann T: Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science. 2000 Dec 15;290(5499):2140-4. [PubMed:11118147]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Activator
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRG
Uniprot ID
P48443
Uniprot Name
Retinoic acid receptor RXR-gamma
Molecular Weight
50870.72 Da
References
  1. German OL, Monaco S, Agnolazza DL, Rotstein NP, Politi LE: Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors. J Lipid Res. 2013 Aug;54(8):2236-46. doi: 10.1194/jlr.M039040. Epub 2013 May 30. [PubMed:23723389]
  2. de Urquiza AM, Liu S, Sjoberg M, Zetterstrom RH, Griffiths W, Sjovall J, Perlmann T: Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science. 2000 Dec 15;290(5499):2140-4. [PubMed:11118147]
  3. Wietrzych-Schindler M, Szyszka-Niagolov M, Ohta K, Endo Y, Perez E, de Lera AR, Chambon P, Krezel W: Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice. Biol Psychiatry. 2011 Apr 15;69(8):788-94. doi: 10.1016/j.biopsych.2010.12.017. Epub 2011 Feb 21. [PubMed:21334601]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function
Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By sim...
Gene Name
SREBF1
Uniprot ID
P36956
Uniprot Name
Sterol regulatory element-binding protein 1
Molecular Weight
121673.6 Da
References
  1. Patterson E, Wall R, Fitzgerald GF, Ross RP, Stanton C: Health implications of high dietary omega-6 polyunsaturated Fatty acids. J Nutr Metab. 2012;2012:539426. doi: 10.1155/2012/539426. Epub 2012 Apr 5. [PubMed:22570770]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Yao HT, Chang YW, Lan SJ, Chen CT, Hsu JT, Yeh TK: The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes. Life Sci. 2006 Nov 25;79(26):2432-40. Epub 2006 Aug 23. [PubMed:16978661]

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 July 02, 2018 20:57