ICOSAPENT ETHYL

First approved in 2008

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H34O2
Molecular Weight	330.5042
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	5
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC

InChI

InChIKey=SSQPWTVBQMWLSZ-AAQCHOMXSA-N

InChI=1S/C22H34O2/c1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24-4-2/h5-6,8-9,11-12,14-15,17-18H,3-4,7,10,13,16,19-21H2,1-2H3/b6-5-,9-8-,12-11-,15-14-,18-17-

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00159
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000Lbl.pdf

Icosapent is an 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. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
GO:0004144 diacylglycerol O-acyltransferase activity 4 Target ID: GO:0004144 diacylglycerol O-acyltransferase activity Sources: https://www.vascepa.com/assets/pdf/Vascepa_PI.pdf \| https://adisinsight.springer.com/drugs/800015122 \| https://www.ncbi.nlm.nih.gov/pubmed/27444154	Inhibitor 8297
GO:0004465 lipoprotein lipase activity 4 Target ID: GO:0004465 lipoprotein lipase activity Sources: https://www.vascepa.com/assets/pdf/Vascepa_PI.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/27444154	Activator 1430
fatty acid beta-oxidation 4 Target ID: GO:0006635 Sources: https://www.vascepa.com/assets/pdf/Vascepa_PI.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/27444154	Activator 1430
lipoprotein oxidation 4 Target ID: GO:0042161 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26945158	Inhibitor 8297	2.5 µM [IC50]
transformed cell apoptotic process 108 Target ID: GO:0006927 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26295255	Activator 1430	35.0 µM [IC50]
Peroxisome proliferator-activated receptor delta 29 Target ID: CHEMBL3979 Sources: http://www.drugbank.ca/drugs/DB00159	Agonist 2678
Prolyl endopeptidase 9 Target ID: CHEMBL3202 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16478242	Inhibitor 8297	247.5 µM [Ki]
Receptor-mediated non-selective cation current (Icat) 4 Target ID: Receptor-mediated non-selective cation current (Icat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9105714	Inhibitor 8297	7.0 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: http://www.drugbank.ca/drugs/DB00159	Inhibitor 8297
Peroxisome proliferator-activated receptor gamma 111 Target ID: CHEMBL235 Sources: http://www.drugbank.ca/drugs/DB00159	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Hypertriglyceridemia 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000Lbl.pdf	Primary	Approved 8429	Vascepa Approved Use Indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia. Launch Date 2012
Major depressive disorder 173 Sources: https://clinicaltrials.gov/ct2/show/NCT02553915	Primary	Phase III 656	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://clinicaltrials.gov/ct2/show/NCT02719327	Primary	Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
347 μg/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/25428605/	4 g 2 times / day steady-state, oral dose: 4 g route of administration: Oral experiment type: STEADY-STATE co-administered:		ICOSAPENT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
6.519 μg × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/25428605/	4 g 2 times / day steady-state, oral dose: 4 g route of administration: Oral experiment type: STEADY-STATE co-administered:		ICOSAPENT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
89 h REVIEW https://pubmed.ncbi.nlm.nih.gov/25428605/	4 g 2 times / day steady-state, oral dose: 4 g route of administration: Oral experiment type: STEADY-STATE co-administered:		ICOSAPENT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% REVIEW https://pubmed.ncbi.nlm.nih.gov/25428605/	4 g 2 times / day steady-state, oral dose: 4 g route of administration: Oral experiment type: STEADY-STATE co-administered:		ICOSAPENT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inhibitor 1767 inducer 389

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP2C8 911 CYP2B6 810 P-gp 1461 BCRP 699 OCT2 647 OAT1 599 OATP1B1 788 OATP1B3 706 OAT3 642	P-gp 1537 BCRP 561 OCT2 355 OAT1 326 OATP1B1 406 OATP1B3 350 OAT3 339 CYP 270	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=32 Page: 32.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=32 Page: 32.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=32 Page: 32.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=32 Page: 32.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=32 Page: 32.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=32 Page: 32.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27.0	no	no (co-administration study) Comment: Vascepa did not affect the AUC or Cmax of exposure of racemic warfarin; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202057s035lbl.pdf Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27.0
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27.0	no	no (co-administration study) Comment: Vascepa did not affect the AUC or Cmax of exposure of atorvastatin; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202057s035lbl.pdf Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27.0
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27;28	weak [IC50 12.8 uM]	no (co-administration study) Comment: Vascepa did not affect the AUC or Cmax of exposure of rosiglitazone; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202057s035lbl.pdf Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27;28
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27;28	weak [IC50 14 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27;28	weak [IC50 14 uM]	no (co-administration study) Comment: Vascepa did not affect the AUC or Cmax of exposure of racemic warfarin; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202057s035lbl.pdf Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27;28
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27;28	weak [IC50 8.4 uM]	no (co-administration study) Comment: Vascepa did not affect the AUC or Cmax of exposure of omeprazole; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202057s035lbl.pdf Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=27 Page: 27;28
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000PharmR.pdf#page=32 Page: 32.0	yes [Inhibition 1 uM]

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000ClinPharmR.pdf#page=14 Page: 14.0	no
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000ClinPharmR.pdf#page=14 Page: 14.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000ClinPharmR.pdf#page=14 Page: 14.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000ClinPharmR.pdf#page=14 Page: 14.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000ClinPharmR.pdf#page=14 Page: 14.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000ClinPharmR.pdf#page=14 Page: 14.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202057Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	no

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA0037XT	https://www.aablocks.com/goods/Goods/detail?id=AA0037XT
AHH Chemical co.,ltd	MT-11661	http://www.ahhchemical.com/product/MT-11661.html
AK Scientific, Inc. (AKSCI)	1755AH	http://www.aksci.com/item_detail.php?cat=1755AH
Aaron Chemicals	AR0038PL	http://www.aaronchem.com/10417-94-4
AbMole Bioscience	M5608	http://www.abmole.com/products/eicosapentaenoic-acid.html
Alfa Chemistry	AP10417944	https://reagents.alfa-chemistry.com/product/cis-5-8-11-14-17-eicosapentaenoic-acid-cas-10417-94-4-988.html
Alfa Chemistry	10417-94-4	https://www.alfa-chemistry.com/epa-cas-10417-94-4-item-289473.htm
Alichem	490013200	http://www.alichem.com/en/products/10417-94-4.html
Allbio Pharm Co., Ltd	AB00247	http://www.allbiopharm.com/product/n/AB00247
Alsachim	978	http://www.alsachim.com/product-C3217-glo.bal-view.html
Aurora Fine Chemicals LLC	A17.876.800	http://online.aurorafinechemicals.com/info?ID=A17.876.800
AvaChem Scientific	6305	https://www.avachem.com/productSearch.asp?6305
BLD Pharm	BD127342	http://www.bldpharm.com/products/10417-94-4.html
BioSynth	J-001125	https://www.biosynth.com/en/products/all-products/products/J-001125.html
CSNpharm	CSN10913	https://www.csnpharm.com/products/eicosapentaenoic-acid.html
Calbiochem	324875	http://www.emdbiosciences.com/product/324875
Chem Scene	CS-2895	http://www.chemscene.com/10417-94-4.html
Chemenu	CM126647	http://www.chemenu.com/products/CM126647
Chemspace	CSSB00016999425	https://chem-space.com/CSSB00016999425
DC Chemicals	DC31714	http://www.dcchemicals.com//product_show-Icosapent.html
EMD Millipore	324875	http://www.emdbiosciences.com/product/324875
Glentham Life Sciences	GK4054	http://www.glentham.com/products/product/GK4054/
Lab Network	LN01307220	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01307220
MedChem Express	HY-B0660	https://www.medchemexpress.com/Eicosapentaenoic-Acid.html
MuseChem	I000242	https://www.musechem.com/product/I000242.html
Sigma-Aldrich	E-113_CERILLIAN	https://www.sigmaaldrich.com/catalog/product/cerillian/e113?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	44864_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/44864?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	E2011_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/e2011?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	E7006_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/e7006?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S530376	http://www.smolecule.com/products/s530376
TCI (Tokyo Chemical Industry)	E0441	http://www.tcichemicals.com/eshop/en/us/commodity/E0441/index.html
THE BioTek	bt-269997	https://www.thebiotek.com/product/inhibitors/bt-269997
Tocris	5979	https://www.tocris.com/products/eicosapentaenoic-acid_5979
VladaChem	VL261029-100MG	https://www.vladachem.com/product.php?products=10417-94-4
abcr GmbH	AB135514	http://www.abcr.com/shop/en/AB135514
iChemical	EBD219836	http://www.ichemical.com/products/10417-94-4.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
[Decreasing atherogenic risks by an eicosapentaenoic acid-rich diet].	1987 Mar 1	3035811
Effects of small concentrations of eicosapentaenoic acid on platelets.	1989	2539831
Lower levels of lipid peroxidation in human platelets incubated with eicosapentaenoic acid.	1992 Jul 29	1643099
Regulation of rat liver apolipoprotein A-I, apolipoprotein A-II and acyl-coenzyme A oxidase gene expression by fibrates and dietary fatty acids.	1995 Aug 15	7556148
Dietary fish oil decreases superoxide generation by human neutrophils: relation to cyclooxygenase pathway and lysosomal enzyme release.	1996 Sep	8931114
Modulation in vitro of human natural cytotoxicity, lymphocyte proliferative response to mitogens and cytokine production by essential fatty acids.	1997 Oct	9415022
The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells.	2001 Jan	11172467
Discovery of gemifloxacin (Factive, LB20304a): a quinolone of a new generation.	2001 Jan-Feb	11347965
Organotropic chemopreventive effects of n-3 unsaturated fatty acids in a rat multi-organ carcinogenesis model.	2001 Nov	11714441
Eicosapentaenoic acid and gamma-linolenic acid induce apoptosis in HL-60 cells.	2002 Sep	12384078
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.	2003 Feb 20	12573452
Polyunsaturated fatty acids block dendritic cell activation and function independently of NF-kappaB activation.	2005 Apr 8	15684433
Fatty acids and expression of adipokines.	2005 May 30	15949695
Mechanism of induction of muscle protein degradation by angiotensin II.	2006 Jul	16257180
Conjugated linoleic acid, unlike other unsaturated fatty acids, strongly induces glutathione synthesis without any lipoperoxidation.	2006 Nov	17092368
The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes.	2006 Nov 25	16978661
Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program.	2007 Feb	17237316
n-3 fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet.	2009 May	19277604
Docosahexaenoic acid increases cellular adiponectin mRNA and secreted adiponectin protein, as well as PPARγ mRNA, in 3T3-L1 adipocytes.	2010 Dec	21164549
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).	2011 Sep 1	21683321
Additive, antagonistic, and synergistic effects of procyanidins and polyunsaturated fatty acids over inflammation in RAW 264.7 macrophages activated by lipopolysaccharide.	2012 Apr	22169119
Elevated blood pressure in cytochrome P4501A1 knockout mice is associated with reduced vasodilation to omega-3 polyunsaturated fatty acids.	2012 Nov 1	22995157
Fish oil and fenofibrate prevented phosphorylation-dependent hepatic sortilin 1 degradation in Western diet-fed mice.	2014 Aug 8	24986865

Patents

Sample Use Guides

In Vivo Use Guide

The daily dose of VASCEPA ( (icosapent) is 4 grams per day taken as 2 capsules twice daily with food.

Route of Administration: Oral

In Vitro Use Guide

The approximate 50% inhibitory concentrations (IC50) of EPA on LA-N-1 cells at 48 hours treatment was found to be 35 uM, whereas the IC50 for ALA on LA-N-1 cells at 48 hours treatment was found to be >50 uM.

Name

Type

Language

ICOSAPENT ETHYL

Official Name

English

AMR-101

Code

English

EICOSAPENTAENOIC ACID ETHYL ESTER

Systematic Name

English

AMR 101

Code

English

Eicosapentaenoic acid ethyl ester [WHO-DD]

Common Name

English

ETHYL EICOSAPENTAENOIC ACID

Systematic Name

English

ICOSAPENT ETHYL [ORANGE BOOK]

Common Name

English

VASCEPA

Brand Name

English

ETHYL ICOSAPENT

Common Name

English

ETHYL ICOSAPENTATE

Common Name

English

ETHYL EICOSAPENTAENOATE

Systematic Name

English

EICOSAPENTAENOIC ACID ETHYL ESTER [MART.]

Common Name

English

5,8,11,14,17-EICOSAPENTAENOIC ACID, ETHYL ESTER, (5Z,8Z,11Z,14Z,17Z)-

Common Name

English

ETHYL ALL-CIS-5,8,11,14,17-ICOSAPENTAENOIC ACID

Common Name

English

TIMNODONIC ACID ETHYL ESTER

Common Name

English

NSC-759597

Code

English

AMR101

Code

English

EPADEL

Common Name

English

ICOSAPENT ETHYL [VANDF]

Common Name

English

Ethyl (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoate

Systematic Name

English

ICOSAPENT ETHYL [USAN]

Common Name

English

EICOSAPENTAENOIC ACID ETHYL ESTER [USP-RS]

Common Name

English

EICOSAPENTAENOIC ACID ETHYL ESTER [MI]

Common Name

English

ICOSAPENT ETHYL ESTER

Common Name

English

ETHYL ICOSAPENTATE [JAN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

134300