Identification

Name
Icosapent
Accession Number
DB00159  (NUTR00024)
Type
Small Molecule
Groups
Approved, Nutraceutical
Description

Important polyunsaturated fatty acid found in fish oils. It serves as the precursor for the prostaglandin-3 and thromboxane-3 families. A diet rich in eicosapentaenoic acid lowers serum lipid concentration, reduces incidence of cardiovascular disorders, prevents platelet aggregation, and inhibits arachidonic acid conversion into the thromboxane-2 and prostaglandin-2 families. [PubChem]

Structure
Thumb
Synonyms
  • (5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-Eicosapentaenoic acid
  • (5Z,8Z,11Z,14Z,17Z)-Eicosapentaenoate
  • (5Z,8Z,11Z,14Z,17Z)-Eicosapentaenoic acid
  • (5Z,8Z,11Z,14Z,17Z)-Icosapentaenoic acid
  • (all-Z)-5,8,11,14,17-Eicosapentaenoic acid
  • 5,8,11,14,17-EICOSAPENTAENOIC acid
  • 5,8,11,14,17-Icosapentaenoic acid
  • all-cis-5,8,11,14,17-eicosapentaenoic acid
  • all-cis-5,8,11,14,17-icosapentaenoic acid
  • all-cis-icosa-5,8,11,14,17-pentaenoic acid
  • cis-5,8,11,14,17-Eicosapentaenoic acid
  • cis-5,8,11,14,17-EPA
  • cis-delta(5,8,11,14,17)-Eicosapentaenoic acid
  • cis, cis, cis, cis, cis-Eicosa-5,8,11,14,17-pentaenoic acid
  • Eicosapentaenoic acid
  • EPA
  • Icosapent
  • Icosapentaenoic acid
  • Icosapento
  • Icosapentum
  • Timnodonic acid
External IDs
EPA 45G
Product Ingredients
IngredientUNIICASInChI Key
Icosapent sodium5PXN91KPRO73167-03-0RBZYGQJEMWGTOH-RSDXMDNYSA-M
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Animi-3Icosapent (35 mg/1) + Cholecalciferol (1000 [iU]/1) + Cyanocobalamin (500 ug/1) + Doconexent (250 mg/1) + Folic Acid (1 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 DIcosapent (35 mg/1) + Cholecalciferol (1000 [iU]/1) + Cyanocobalamin (500 ug/1) + Doconexent (250 mg/1) + Folic Acid (1 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 AssureIcosapent + DoconexentKitMission Pharmacal2014-04-30Not applicableUs
Folcaps Care OneIcosapent (100 mg/1) + Alpha-Linolenic Acid (50 mg/1) + Biotin (300 mg/1) + Calcium Carbonate (100 mg/1) + Calcium threonate (1 mg/1) + Cholecalciferol (800 [iU]/1) + Doconexent (350 mg/1) + Docusate sodium (50 mg/1) + Folic Acid (1 mg/1) + Iodine (150 ug/1) + Iron (27 mg/1) + Magnesium (50 mg/1) + Nicotinamide (10 mg/1) + Pyridoxine hydrochloride (50 mg/1) + Riboflavin (1.5 mg/1) + Calcium ascorbate (24 mg/1) + Vitamin E acetate (15 [iU]/1) + Zinc (5 mg/1)Capsule, gelatin coatedOralMidlothian Laboratories2009-05-01Not applicableUs
Folcaps Omega-3Icosapent (40 mg/1) + Alpha-Linolenic Acid (30 mg/1) + Calcium (150 mg/1) + Calcium threonate (1 mg/1) + Cholecalciferol (170 [iU]/1) + Doconexent (260 mg/1) + Ferrous asparto glycinate (7 mg/1) + Folic Acid (1 mg/1) + Iron (20 mg/1) + Pyridoxine hydrochloride (25 mg/1) + Calcium ascorbate (24 mg/1) + Vitamin E acetate (30 [iU]/1)Capsule, gelatin coatedOralMidlothian Laboratories2011-01-03Not applicableUs
Gesticare DHAIcosapent + Calcium Carbonate + Cholecalciferol + Choline bitartrate + Cyanocobalamin + Doconexent + Folic Acid + Ferrous fumarate + Niacin + Potassium Iodide + Pyridoxine hydrochloride + Riboflavin + Thiamine mononitrate + Vitamin C + Vitamin E acetate + Zinc oxideKitJazz Pharmaceuticals Commercial Corp.2008-10-01Not applicableUs
HerbalifelineIcosapent (119 mg) + Docosahexaenoate (78 mg)CapsuleOralHerbalife International Of Luxembourg S À R L2004-07-192009-07-21Canada
Natelle OneIcosapent (.625 mg/1) + Calcium phosphate, tribasic (100 mg/1) + Doconexent (250 mg/1) + Folic Acid (1 mg/1) + Ferrous fumarate (27 mg/1) + Pyridoxine hydrochloride (25 mg/1) + Vitamin C (30 mg/1) + Vitamin E (30 [iU]/1)Capsule, gelatin coatedOralAzur Pharma, Inc.2009-11-09Not applicableUs
Natelle OneIcosapent (.625 mg/1) + Calcium phosphate, tribasic (102 mg/1) + Doconexent (250 mg/1) + Folic Acid (1 mg/1) + Ferrous fumarate (28 mg/1) + Pyridoxine hydrochloride (25 mg/1) + Vitamin C (30 mg/1) + Vitamin E (30 [iU]/1)Capsule, gelatin coatedOralJazz Pharmaceuticals Commercial Corp.2010-06-11Not applicableUs
Natelle OneIcosapent (.625 mg/1) + Calcium (102 mg/1) + Doconexent (250 mg/1) + Folic Acid (1 mg/1) + Iron (28 mg/1) + Pyridoxine (25 mg/1) + Vitamin C (30 mg/1) + Vitamin E (30 [iU]/1)Capsule, gelatin coatedOralMeda Pharmaceuticals Ltd2015-02-01Not applicableUs
Categories
UNII
AAN7QOV9EA
CAS number
10417-94-4
Weight
Average: 302.451
Monoisotopic: 302.224580204
Chemical Formula
C20H30O2
InChI Key
JAZBEHYOTPTENJ-JLNKQSITSA-N
InChI
InChI=1S/C20H30O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20(21)22/h3-4,6-7,9-10,12-13,15-16H,2,5,8,11,14,17-19H2,1H3,(H,21,22)/b4-3-,7-6-,10-9-,13-12-,16-15-
IUPAC Name
(5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoic acid
SMILES
CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O

Pharmacology

Indication

EPA can be used for lowering elevated triglycerides in those who are hyperglyceridemic. In addition, EPA may play a therapeutic role in patients with cystic fibrosis by reducing disease severity and may play a similar role in type 2 diabetics in slowing the progression of diabetic nephropathy.

Structured Indications
Not Available
Pharmacodynamics

Eicosanoids are chemical messengers derived from 20-carbon polyunsaturated fatty acids that play critical roles in immune and inflammatory responses. Both 20-carbon omega-6 fatty acids (arachidonic acid) and 20-carbon omega-3 fatty acids (EPA) can be found in cell membranes. During an inflammatory response, arachidonic acid and EPA are metabolized by enzymes known as cyclooxygenases and lipoxygenases to form eicosanoids. Increasing omega-3 fatty acid intake increases the EPA content of cell membranes and decreases the arachidonic acid content, resulting in higher proportions of eicosanoids derived from EPA. Physiologic responses to arachidonic acid-derived eicosanoids differ from responses to EPA-derived eicosanoids. In general, eicosanoids derived from EPA are less potent inducers of inflammation, blood vessel constriction, and clotting than eicosanoids derived from arachidonic acid.

Mechanism of action

The anti-inflammatory, antithrombotic and immunomodulatory actions of EPA is probably due to its role in eicosanoid physiology and biochemistry. Most eicosanoids are produced by the metabolism of omega-3 fatty acids, specifically, arachidonic acid. These eicosanoids, leukotriene B4 (LTB4) and thromboxane A2 (TXA2) stimulate leukocyte chemotaxis, platelet aggregation and vasoconstriction. They are thrombogenic and artherogenic. On the other hand, EPA is metabolized to leukotriene B5 (LTB5) and thromboxane A3 (TXA3), which are eicosanoids that promote vasodilation, inhibit platelet aggregation and leukocyte chemotaxis and are anti-artherogenic and anti-thrombotic. The triglyceride-lowering effect of EPA results from inhibition of lipogenesis and stimulation of fatty acid oxidation. Fatty acid oxidation of EPA occurs mainly in the mitochondria. EPA is a substrate for Prostaglandin-endoperoxide synthase 1 and 2. It also appears to affect the function and bind to the Carbohydrate responsive element binding protein (ChREBP) and to a fatty acid receptor (G-coupled receptor) known as GP40.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Human
AProstaglandin G/H synthase 1
inhibitor
Human
APeroxisome proliferator-activated receptor gamma
agonist
Human
APeroxisome proliferator-activated receptor delta
agonist
Human
UFatty acid desaturase 1
agonist
Human
ULong-chain-fatty-acid--CoA ligase 4
inducer
Human
ULong-chain-fatty-acid--CoA ligase 3
inducer
Human
AFree fatty acid receptor 1
agonist
Human
ASodium/calcium exchanger 1
inhibitor
Human
UTransient receptor potential cation channel subfamily V member 1
inducer
Human
UPeroxisome proliferator-activated receptor alphaNot 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
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

Akira Seto, Shoko Yamashita, "Method of preparing fatty acid composition containing high concentration of eicosapentaenoic acid." U.S. Patent US4615839, issued March, 1983.

US4615839
General References
  1. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN: Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol. 2011 Sep 1;108(5):682-90. doi: 10.1016/j.amjcard.2011.04.015. Epub 2011 Jun 16. [PubMed:21683321]
External Links
Human Metabolome Database
HMDB01999
KEGG Drug
D08061
KEGG Compound
C06428
PubChem Compound
446284
PubChem Substance
46506267
ChemSpider
393682
BindingDB
50242349
ChEBI
28364
ChEMBL
CHEMBL460026
Therapeutic Targets Database
DAP000969
PharmGKB
PA164746077
IUPHAR
3362
Guide to Pharmacology
GtP Drug Page
HET
EPA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Eicosapentaenoic_acid
PDB Entries
1igx / 3gwx / 3hs6 / 5m0o
FDA label
Download (173 KB)
MSDS
Download (23.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentMajor Depressive Disorder in Pregnancy2
1Active Not RecruitingTreatmentNeoplasms, Breast / Stage 0 Breast Carcinoma / Stage I Breast Carcinoma / Stage II Breast Carcinoma / Stage III Breast Carcinoma1
1CompletedTreatmentHealthy Volunteers1
2CompletedBasic ScienceAdipose Tissue Inflammation / Obesity, Morbid1
2CompletedTreatmentAcute Lung Injury (ALI) / Acute Respiratory Distress Syndrome (ARDS) / Respiratory Distress Syndrome, Adult1
2CompletedTreatmentBipolar Disorder (BD) / Coronary Artery Disease / Major Depressive Disorder (MDD) / Schizoaffective Disorders / Schizophrenic Disorders1
2CompletedTreatmentSubstance-Related Disorders1
2, 3CompletedPreventionFamilial Adenomatous Polyposis Coli / FAP1
2, 3CompletedTreatmentAbstinence Syndrome / Behavior, Addictive1
2, 3CompletedTreatmentAdenomatous Polyps1
2, 3CompletedTreatmentPsychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorders1
2, 3RecruitingTreatmentBMI >27 kg/m2 / BMI >30 kg/m2 / Inflammatory Reaction / Major Depressive Disorder (MDD)1
3CompletedTreatmentAge-Related Macular Degeneration (ARMD) / Cataracts1
3CompletedTreatmentCardiovascular Disease (CVD) / Inflammatory Reaction1
3CompletedTreatmentCoronary Heart Disease (CHD) / Myocardial Infarction (MI)1
3CompletedTreatmentHypertriglyceridemias1
3RecruitingTreatmentTransplantation, Kidney1
3TerminatedPreventionCoronary Artery Disease / Type 2 Diabetes Mellitus1
3Unknown StatusTreatmentCancer treatment / Colorectal Cancers / Malignant Neoplasm of Stomach1
3Unknown StatusTreatmentRheumatoid Arthritis1
4Active Not RecruitingPreventionMalignant Neoplasm of Colon1
4Active Not RecruitingTreatmentObesity, Morbid1
4CompletedTreatmentCoronary Artery Disease Progression1
4CompletedTreatmentDyskinesias / Schizophrenic Disorders1
4RecruitingTreatmentBMI >30 kg/m2 / Esophagus, Barrett1
4Unknown StatusTreatmentArrythmias / Coronary Artery Disease1
Not AvailableActive Not RecruitingPreventionAutoimmune Diseases / Knee Pain Chronic / Osteoarthritis (OA) / Rheumatoid Arthritis / Systemic Inflammatory Process1
Not AvailableActive Not RecruitingPreventionType 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentCancer Cachexia1
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus1
Not AvailableEnrolling by InvitationPreventionAdiposity1
Not AvailableRecruitingBasic ScienceHyperlipidemias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • V Sab Medical Labs Inc.
Dosage forms
FormRouteStrength
CapsuleOral
Kit
Capsule, gelatin coatedOral
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
logP6.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000289 mg/mLALOGPS
logP6.53ALOGPS
logP6.23ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)4.82ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity101.07 m3·mol-1ChemAxon
Polarizability35.93 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9896
Blood Brain Barrier+0.9314
Caco-2 permeable+0.7735
P-glycoprotein substrateNon-substrate0.6766
P-glycoprotein inhibitor INon-inhibitor0.9499
P-glycoprotein inhibitor IINon-inhibitor0.9025
Renal organic cation transporterNon-inhibitor0.9311
CYP450 2C9 substrateNon-substrate0.7735
CYP450 2D6 substrateNon-substrate0.9081
CYP450 3A4 substrateNon-substrate0.6884
CYP450 1A2 substrateInhibitor0.6915
CYP450 2C9 inhibitorNon-inhibitor0.8798
CYP450 2D6 inhibitorNon-inhibitor0.9631
CYP450 2C19 inhibitorNon-inhibitor0.9638
CYP450 3A4 inhibitorNon-inhibitor0.9465
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9426
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6502
BiodegradationReady biodegradable0.7808
Rat acute toxicity1.4499 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8818
hERG inhibition (predictor II)Non-inhibitor0.9315
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-9700000000-09ea61ed836b88205028
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-MSGC-MSsplash10-004l-9700000000-09ea61ed836b88205028
Mass Spectrum (Electron Ionization)MSsplash10-05ox-9400000000-567226e93d65502352cd
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/MSsplash10-0udi-0029000000-02c67e3601df249d2476

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
omega-3 fatty acid, icosapentaenoic acid (CHEBI:28364) / Unsaturated fatty acids, Polyunsaturated fatty acids, Liner triterpenes (C06428) / Unsaturated fatty acids (LMFA01030759)

Targets

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. 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. Lee JY, Plakidas A, Lee WH, Heikkinen A, Chanmugam P, Bray G, Hwang DH: Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res. 2003 Mar;44(3):479-86. Epub 2002 Dec 1. [PubMed:12562875]
  2. Ait-Said F, Elalamy I, Werts C, Gomard MT, Jacquemin C, Couetil JP, Hatmi M: Inhibition by eicosapentaenoic acid of IL-1beta-induced PGHS-2 expression in human microvascular endothelial cells: involvement of lipoxygenase-derived metabolites and p38 MAPK pathway. Biochim Biophys Acta. 2003 Feb 20;1631(1):77-84. [PubMed:12573452]
  3. Machida T, Hiramatsu M, Hamaue N, Minami M, Hirafuji M: Docosahexaenoic acid enhances cyclooxygenase-2 induction by facilitating p44/42, but not p38, mitogen-activated protein kinase activation in rat vascular smooth muscle cells. J Pharmacol Sci. 2005 Sep;99(1):113-6. Epub 2005 Sep 1. [PubMed:16141635]
  4. 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]
  5. Chene G, Dubourdeau M, Balard P, Escoubet-Lozach L, Orfila C, Berry A, Bernad J, Aries MF, Charveron M, Pipy B: n-3 and n-6 polyunsaturated fatty acids induce the expression of COX-2 via PPARgamma activation in human keratinocyte HaCaT cells. Biochim Biophys Acta. 2007 May;1771(5):576-89. Epub 2007 Mar 16. [PubMed:17459764]
  6. Vecchio AJ, Simmons DM, Malkowski MG: Structural basis of fatty acid substrate binding to cyclooxygenase-2. J Biol Chem. 2010 Jul 16;285(29):22152-63. doi: 10.1074/jbc.M110.119867. Epub 2010 May 12. [PubMed:20463020]
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. 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]
  2. Machida T, Hiramatsu M, Hamaue N, Minami M, Hirafuji M: Docosahexaenoic acid enhances cyclooxygenase-2 induction by facilitating p44/42, but not p38, mitogen-activated protein kinase activation in rat vascular smooth muscle cells. J Pharmacol Sci. 2005 Sep;99(1):113-6. Epub 2005 Sep 1. [PubMed:16141635]
  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. 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]
  5. Yang P, Chan D, Felix E, Cartwright C, Menter DG, Madden T, Klein RD, Fischer SM, Newman RA: Formation and antiproliferative effect of prostaglandin E(3) from eicosapentaenoic acid in human lung cancer cells. J Lipid Res. 2004 Jun;45(6):1030-9. Epub 2004 Mar 1. [PubMed:14993240]
  6. Vecchio AJ, Simmons DM, Malkowski MG: Structural basis of fatty acid substrate binding to cyclooxygenase-2. J Biol Chem. 2010 Jul 16;285(29):22152-63. doi: 10.1074/jbc.M110.119867. Epub 2010 May 12. [PubMed:20463020]
  7. Lee JY, Plakidas A, Lee WH, Heikkinen A, Chanmugam P, Bray G, Hwang DH: Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res. 2003 Mar;44(3):479-86. Epub 2002 Dec 1. [PubMed:12562875]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. Chambrier C, Bastard JP, Rieusset J, Chevillotte E, Bonnefont-Rousselot D, Therond P, Hainque B, Riou JP, Laville M, Vidal H: Eicosapentaenoic acid induces mRNA expression of peroxisome proliferator-activated receptor gamma. Obes Res. 2002 Jun;10(6):518-25. [PubMed:12055328]
  2. Selvaraj RK, Klasing KC: Lutein and eicosapentaenoic acid interact to modify iNOS mRNA levels through the PPARgamma/RXR pathway in chickens and HD11 cell lines. J Nutr. 2006 Jun;136(6):1610-6. [PubMed:16702329]
  3. Iwata Y, Miyamoto S, Takamura M, Yanagisawa H, Kasuya A: Interaction between peroxisome proliferator-activated receptor gamma and its agonists: docking study of oximes having 5-benzyl-2,4-thiazolidinedione. J Mol Graph Model. 2001;19(6):536-42, 598-600. [PubMed:11552681]
  4. Horia E, Watkins BA: Complementary actions of docosahexaenoic acid and genistein on COX-2, PGE2 and invasiveness in MDA-MB-231 breast cancer cells. Carcinogenesis. 2007 Apr;28(4):809-15. Epub 2006 Oct 19. [PubMed:17052999]
  5. Ramakers JD, Mensink RP, Schaart G, Plat J: Arachidonic acid but not eicosapentaenoic acid (EPA) and oleic acid activates NF-kappaB and elevates ICAM-1 expression in Caco-2 cells. Lipids. 2007 Aug;42(8):687-98. Epub 2007 Jul 3. [PubMed:17610002]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-lin...
Gene Name
PPARD
Uniprot ID
Q03181
Uniprot Name
Peroxisome proliferator-activated receptor delta
Molecular Weight
49902.99 Da
References
  1. Iwata Y, Miyamoto S, Takamura M, Yanagisawa H, Kasuya A: Interaction between peroxisome proliferator-activated receptor gamma and its agonists: docking study of oximes having 5-benzyl-2,4-thiazolidinedione. J Mol Graph Model. 2001;19(6):536-42, 598-600. [PubMed:11552681]
  2. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, Sternbach DD, Lehmann JM, Wisely GB, Willson TM, Kliewer SA, Milburn MV: Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999 Mar;3(3):397-403. [PubMed:10198642]
  3. Kondo H, Misaki R, Gelman L, Watabe S: Ligand-dependent transcriptional activities of four torafugu pufferfish Takifugu rubripes peroxisome proliferator-activated receptors. Gen Comp Endocrinol. 2007 Oct-Dec;154(1-3):120-7. Epub 2007 Jun 12. [PubMed:17632107]
  4. Inoue I, Shino K, Noji S, Awata T, Katayama S: Expression of peroxisome proliferator-activated receptor alpha (PPAR alpha) in primary cultures of human vascular endothelial cells. Biochem Biophys Res Commun. 1998 May 19;246(2):370-4. [PubMed:9610365]
  5. Caldari-Torres C, Rodriguez-Sallaberry C, Greene ES, Badinga L: Differential effects of n-3 and n-6 fatty acids on prostaglandin F2alpha production by bovine endometrial cells. J Dairy Sci. 2006 Mar;89(3):971-7. [PubMed:16507691]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Oxidoreductase activity
Specific Function
Isoform 2 does not exhibit any catalytic activity toward 20:3n-6, but it may enhance FADS2 activity (By similarity). Isoform 1 is a component of a lipid metabolic pathway that catalyzes biosynthesi...
Gene Name
FADS1
Uniprot ID
O60427
Uniprot Name
Fatty acid desaturase 1
Molecular Weight
51963.945 Da
References
  1. Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH: Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr. 2000 Aug;130(8):1925-31. [PubMed:10917903]
  2. Navarro E, Esteve M, Olive A, Klaassen J, Cabre E, Tena X, Fernandez-Banares F, Pastor C, Gassull MA: Abnormal fatty acid pattern in rheumatoid arthritis. A rationale for treatment with marine and botanical lipids. J Rheumatol. 2000 Feb;27(2):298-303. [PubMed:10685788]
  3. Engler MM, Bellenger-Germain SH, Engler MB, Narce MM, Poisson JP: Dietary docosahexaenoic acid affects stearic acid desaturation in spontaneously hypertensive rats. Lipids. 2000 Sep;35(9):1011-5. [PubMed:11026622]
  4. Chavali SR, Zhong WW, Forse RA: Dietary alpha-linolenic acid increases TNF-alpha, and decreases IL-6, IL-10 in response to LPS: effects of sesamin on the delta-5 desaturation of omega6 and omega3 fatty acids in mice. Prostaglandins Leukot Essent Fatty Acids. 1998 Mar;58(3):185-91. [PubMed:9610840]
  5. Watts JL, Browse J: Isolation and characterization of a Delta 5-fatty acid desaturase from Caenorhabditis elegans. Arch Biochem Biophys. 1999 Feb 1;362(1):175-82. [PubMed:9917342]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Very long-chain fatty acid-coa ligase activity
Specific Function
Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses arachidonate and eicosapentaenoate as substrates.
Gene Name
ACSL4
Uniprot ID
O60488
Uniprot Name
Long-chain-fatty-acid--CoA ligase 4
Molecular Weight
79187.38 Da
References
  1. Heimli H, Hollung K, Drevon CA: Eicosapentaenoic acid-induced apoptosis depends on acyl CoA-synthetase. Lipids. 2003 Mar;38(3):263-8. [PubMed:12784866]
  2. Covault J, Pettinati H, Moak D, Mueller T, Kranzler HR: Association of a long-chain fatty acid-CoA ligase 4 gene polymorphism with depression and with enhanced niacin-induced dermal erythema. Am J Med Genet B Neuropsychiatr Genet. 2004 May 15;127B(1):42-7. [PubMed:15108178]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Protein kinase binding
Specific Function
Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. ACSL3 mediates hepatic lipogenesis (By similarity). Preferent...
Gene Name
ACSL3
Uniprot ID
O95573
Uniprot Name
Long-chain-fatty-acid--CoA ligase 3
Molecular Weight
80419.415 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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Lipid binding
Specific Function
G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose-stimulated insul...
Gene Name
FFAR1
Uniprot ID
O14842
Uniprot Name
Free fatty acid receptor 1
Molecular Weight
31456.645 Da
References
  1. Itoh Y, Hinuma S: GPR40, a free fatty acid receptor on pancreatic beta cells, regulates insulin secretion. Hepatol Res. 2005 Oct;33(2):171-3. Epub 2005 Oct 6. [PubMed:16214394]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ion channel binding
Specific Function
Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellul...
Gene Name
SLC8A1
Uniprot ID
P32418
Uniprot Name
Sodium/calcium exchanger 1
Molecular Weight
108546.06 Da
References
  1. Xiao YF, Ke Q, Chen Y, Morgan JP, Leaf A: Inhibitory effect of n-3 fish oil fatty acids on cardiac Na+/Ca2+ exchange currents in HEK293t cells. Biochem Biophys Res Commun. 2004 Aug 13;321(1):116-23. [PubMed:15358223]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Transmembrane signaling receptor activity
Specific Function
Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular aci...
Gene Name
TRPV1
Uniprot ID
Q8NER1
Uniprot Name
Transient receptor potential cation channel subfamily V member 1
Molecular Weight
94955.33 Da
References
  1. Matta JA, Miyares RL, Ahern GP: TRPV1 is a novel target for omega-3 polyunsaturated fatty acids. J Physiol. 2007 Jan 15;578(Pt 2):397-411. Epub 2006 Oct 12. [PubMed:17038422]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Murakami K, Ide T, Suzuki M, Mochizuki T, Kadowaki T: Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha. Biochem Biophys Res Commun. 1999 Jul 14;260(3):609-13. [PubMed:10403814]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Balendiran GK, Schnutgen F, Scapin G, Borchers T, Xhong N, Lim K, Godbout R, Spener F, Sacchettini JC: Crystal structure and thermodynamic analysis of human brain fatty acid-binding protein. J Biol Chem. 2000 Sep 1;275(35):27045-54. [PubMed:10854433]
  2. Liu YE, Pu W, Wang J, Kang JX, Shi YE: Activation of Stat5 and induction of a pregnancy-like mammary gland differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids. FEBS J. 2007 Jul;274(13):3351-62. Epub 2007 Jun 5. [PubMed:17547694]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Pavicevic ID, Jovanovic VB, Takic MM, Penezic AZ, Acimovic JM, Mandic LM: Fatty acids binding to human serum albumin: Changes of reactivity and glycation level of Cysteine-34 free thiol group with methylglyoxal. Chem Biol Interact. 2014 Dec 5;224:42-50. doi: 10.1016/j.cbi.2014.10.008. Epub 2014 Oct 17. [PubMed:25451573]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:34