You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameIcosapent
Accession NumberDB00159  (NUTR00024)
Typesmall molecule
Groupsapproved, 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
SynonymLanguageCode
(5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-Eicosapentaenoic acidNot AvailableNot Available
(5Z,8Z,11Z,14Z,17Z)-EicosapentaenoateNot AvailableNot Available
(5Z,8Z,11Z,14Z,17Z)-Eicosapentaenoic acidNot AvailableNot Available
(5Z,8Z,11Z,14Z,17Z)-Icosapentaenoic acidNot AvailableNot Available
(all-Z)-5,8,11,14,17-Eicosapentaenoic acidNot AvailableNot Available
5,8,11,14,17-EICOSAPENTAENOIC acidNot AvailableNot Available
5,8,11,14,17-Icosapentaenoic acidNot AvailableNot Available
all-cis-5,8,11,14,17-eicosapentaenoic acidNot AvailableNot Available
all-cis-5,8,11,14,17-icosapentaenoic acidNot AvailableNot Available
all-cis-icosa-5,8,11,14,17-pentaenoic acidNot AvailableNot Available
cis-5,8,11,14,17-Eicosapentaenoic acidNot AvailableNot Available
cis-5,8,11,14,17-EPANot AvailableNot Available
cis-delta(5,8,11,14,17)-Eicosapentaenoic acidNot AvailableNot Available
cis, cis, cis, cis, cis-Eicosa-5,8,11,14,17-pentaenoic acidNot AvailableNot Available
Eicosapentaenoic acidNot AvailableNot Available
EPANot AvailableNot Available
IcosapentNot AvailableNot Available
Icosapentaenoic acidNot AvailableNot Available
IcosapentoNot AvailableNot Available
IcosapentumNot AvailableNot Available
Timnodonic acidNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number10417-94-4
WeightAverage: 302.451
Monoisotopic: 302.224580204
Chemical FormulaC20H30O2
InChI KeyJAZBEHYOTPTENJ-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassFatty Acids and Conjugates
SubclassStraight Chain Fatty Acids
Direct parentStraight Chain Fatty Acids
Alternative parentsUnsaturated Fatty Acids; Polyamines; Enolates; Carboxylic Acids
Substituentsenolate; polyamine; carboxylic acid; carboxylic acid derivative
Classification descriptionThis compound belongs to the straight chain fatty acids. These are fatty acids with a straight aliphatic chain.
Pharmacology
IndicationEPA 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.
PharmacodynamicsEicosanoids 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 actionThe 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Alpha Linolenic Acid and Linoleic Acid MetabolismMetabolicSMP00018
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9896
Blood Brain Barrier + 0.9314
Caco-2 permeable + 0.7735
P-glycoprotein substrate Non-substrate 0.6766
P-glycoprotein inhibitor I Non-inhibitor 0.9499
P-glycoprotein inhibitor II Non-inhibitor 0.9025
Renal organic cation transporter Non-inhibitor 0.9311
CYP450 2C9 substrate Non-substrate 0.7735
CYP450 2D6 substrate Non-substrate 0.9081
CYP450 3A4 substrate Non-substrate 0.6884
CYP450 1A2 substrate Inhibitor 0.6915
CYP450 2C9 substrate Non-inhibitor 0.8798
CYP450 2D6 substrate Non-inhibitor 0.9631
CYP450 2C19 substrate Non-inhibitor 0.9638
CYP450 3A4 substrate Non-inhibitor 0.9465
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9426
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.6502
Biodegradation Ready biodegradable 0.7808
Rat acute toxicity 1.4499 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8818
hERG inhibition (predictor II) Non-inhibitor 0.9315
Pharmacoeconomics
ManufacturersNot Available
Packagers
  • V Sab Medical Labs Inc.
Dosage forms
FormRouteStrength
CapsuleOral
PricesNot Available
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
logP6.1Not Available
Predicted Properties
PropertyValueSource
water solubility2.89e-04 g/lALOGPS
logP6.53ALOGPS
logP6.23ChemAxon
logS-6ALOGPS
pKa (strongest acidic)4.82ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area37.3ChemAxon
rotatable bond count13ChemAxon
refractivity101.07ChemAxon
polarizability35.93ChemAxon
number of rings0ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraGC-MS
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 Reference
  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
External Links
ResourceLink
KEGG DrugD08061
KEGG CompoundC06428
ChEBI28364
ChEMBLCHEMBL460026
Therapeutic Targets DatabaseDAP000969
PharmGKBPA164746077
IUPHAR3362
Guide to Pharmacology3362
HETEPA
RxListhttp://www.rxlist.com/epa_eicosapentaenoic_acid/supplements.htm
Drugs.comhttp://www.drugs.com/mtm/epa-fish-oil.html
PDRhealthhttp://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/eic_0104.shtml
WikipediaEicosapentaenoic_acid
ATC CodesC10AX06
AHFS Codes
  • 88:30.00*
PDB Entries
FDA labelshow(173 KB)
MSDSshow(23.2 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

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
  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
  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
  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
  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
  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. Epub 2010 May 12. Pubmed

2. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

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
  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
  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
  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
  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
  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. Epub 2010 May 12. Pubmed
  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

3. Peroxisome proliferator-activated receptor gamma

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Peroxisome proliferator-activated receptor gamma P37231 Details

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
  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
  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
  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
  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

4. Peroxisome proliferator-activated receptor delta

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Peroxisome proliferator-activated receptor delta Q03181 Details

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
  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
  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
  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
  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

5. Fatty acid desaturase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Fatty acid desaturase 1 O60427 Details

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
  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
  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
  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
  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

6. Long-chain-fatty-acid--CoA ligase 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Long-chain-fatty-acid--CoA ligase 4 O60488 Details

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
  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;127(1):42-7. Pubmed

7. Long-chain-fatty-acid--CoA ligase 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Long-chain-fatty-acid--CoA ligase 3 O95573 Details

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
  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

8. Free fatty acid receptor 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Free fatty acid receptor 1 O14842 Details

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

9. Sodium/calcium exchanger 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium/calcium exchanger 1 P32418 Details

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

10. Transient receptor potential cation channel subfamily V member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Transient receptor potential cation channel subfamily V member 1 Q8NER1 Details

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

Carriers

1. Fatty acid-binding protein, brain

Kind: protein

Organism: Human

Pharmacological action: yes

Components

Name UniProt ID Details
Fatty acid-binding protein, brain O15540 Details

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
  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

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08