General Information of Drug (ID: DMMUCG4)

Drug Name
Eicosapentaenoic acid/docosa-hexaenoic acid
Synonyms
Docosahexaenoic acid; Doconexent; Cervonic acid; 6217-54-5; all-cis-DHA; Doconexentum; Doconexento; Doxonexent; (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid; AquaGrow Advantage; all-Z-Docosahexaenoic acid; Martek DHA HM; Ropufa 60; cis-4,7,10,13,16,19-Docosahexaenoic acid; Docosahexaenoate; UNII-ZAD9OKH9JC; (4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid; Docosahexaenoic acid (all-Z); CCRIS 7670; all-cis-4,7,10,13,16,19-Docosahexaenoic acid; ZAD9OKH9JC; all-cis-docosa-4,7,10,13,16,19-hexaenoic acid; CHEMBL367149; Espanova (TN); DOCOSAHEXAENOIC ACID
Indication
Disease Entry ICD 11 Status REF
Hypertriglyceridemia 5C80.1 Approved [1]
Alzheimer disease 8A20 Phase 3 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 328.5
Topological Polar Surface Area (xlogp) 6.2
Rotatable Bond Count (rotbonds) 14
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Half-life
The concentration or amount of drug in body reduced by one-half in 20 hours [3]
Metabolism
The drug is metabolized via the COX-2 and 15-LOX and 5-LOX activity [4]
Chemical Identifiers
Formula
C22H32O2
IUPAC Name
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid
Canonical SMILES
CC/C=C\\C/C=C\\C/C=C\\C/C=C\\C/C=C\\C/C=C\\CCC(=O)O
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-
InChIKey
MBMBGCFOFBJSGT-KUBAVDMBSA-N
Cross-matching ID
PubChem CID
445580
ChEBI ID
CHEBI:28125
CAS Number
6217-54-5
DrugBank ID
DB03756
TTD ID
D0Q5XX
VARIDT ID
DR00274
INTEDE ID
DR0521

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Prostaglandin G/H synthase 1 (COX-1) TT8NGED PGH1_HUMAN Inhibitor [5]
Prostaglandin G/H synthase 2 (COX-2) TTVKILB PGH2_HUMAN Inhibitor [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Major facilitator superfamily domain-containing protein 2A (SLC59A1) DT5G94L NLS1_HUMAN Substrate [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [7]
Prostaglandin G/H synthase 2 (COX-2) DE492CE PGH2_HUMAN Substrate [8]
Prostaglandin G/H synthase 1 (COX-1) DE073H6 PGH1_HUMAN Substrate [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Hypertriglyceridemia
ICD Disease Classification 5C80.1
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Prostaglandin G/H synthase 2 (COX-2) DTT PTGS2 7.93E-04 -0.29 -0.34
Prostaglandin G/H synthase 1 (COX-1) DTT PTGS1 3.97E-03 0.16 0.43
Major facilitator superfamily domain-containing protein 2A (SLC59A1) DTP MFSD2A 3.02E-08 4.21E-01 6.54E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 1.90E-01 -9.81E-03 -5.96E-02
Prostaglandin G/H synthase 2 (COX-2) DME PTGS2 7.93E-04 -2.88E-01 -3.44E-01
Prostaglandin G/H synthase 1 (COX-1) DME PTGS1 3.97E-03 1.56E-01 4.33E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 FDA approves EPANOVA for the treatment of adults with severe hypertriglyceridemia
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1051).
3 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.
4 Keizer RJ, Huitema AD, Schellens JH, Beijnen JH: Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug;49(8):493-507. doi: 10.2165/11531280-000000000-00000.
5 Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.
6 Mfsd2a Is a Transporter for the Essential -3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development. J Biol Chem. 2016 May 13;291(20):10501-14.
7 CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease? Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):99-108.
8 Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases. FASEB J. 2006 Jun;20(8):1097-108.
9 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
10 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
11 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
12 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
13 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
14 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
15 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
16 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
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18 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
19 Peroxidative free radical formation and O-demethylation of etoposide(VP-16) and teniposide(VM-26). Biochem Biophys Res Commun. 1986 Feb 26;135(1):215-20.
20 Structural basis of fatty acid substrate binding to cyclooxygenase-2. J Biol Chem. 2010 Jul 16;285(29):22152-63.
21 Health implications of high dietary omega-6 polyunsaturated Fatty acids. J Nutr Metab. 2012;2012:539426.
22 PharmGKB summary: very important pharmacogene information for PTGS2. Pharmacogenet Genomics. 2011 Sep;21(9):607-13.
23 Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature. 2014 May 22;509(7501):503-6.
24 The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid. Thromb Haemost. 2008 Jul;100(1):70-5.
25 Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000 Oct;40(10):1109-20.
26 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
27 Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium. Curr Med Res Opin. 2006 Jun;22(6):1133-40.
28 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
29 Ouellet M, Percival MD: Effect of inhibitor time-dependency on selectivity towards cyclooxygenase isoforms. Biochem J. 1995 Feb 15;306 ( Pt 1):247-51.
30 Differential binding mode of diverse cyclooxygenase inhibitors. J Mol Graph Model. 2002 Mar;20(5):359-71.
31 Differential metabolism of dihomo-gamma-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2. Biochem J. 2002 Jul 15;365(Pt 2):489-96.
32 Fenbufen based 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones as safer antiinflammatory and analgesic agents. Eur J Med Chem. 2009 Sep;44(9):3798-804.
33 Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44.
34 Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor, etodolac, in a patient with early rheumatoid arthritis. Intern Med. 2007;46(13):1055-8.
35 Pfizer. Product Development Pipeline. March 31 2009.
36 Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo. Exp Nephrol. 2001;9(6):387-96.
37 Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
38 Flurbiprofen, a cyclooxygenase inhibitor, protects mice from hepatic ischemia/reperfusion injury by inhibiting GSK-3 signaling and mitochondrial permeability transition.Mol Med.2012 Sep 25;18:1128-35.
39 Dissociation of airway inflammation and hyperresponsiveness by cyclooxygenase inhibition in allergen challenged mice. Eur Respir J. 2009 Jul;34(1):200-8.