Details of the Drug

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
Logarithm of the Partition Coefficient (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
CHEMBL367149
CAS Number
6217-54-5
UNII
ZAD9OKH9JC
DrugBank ID
DB03756
TTD ID
D0Q5XX
VARIDT ID
DR00274
INTEDE ID
DR0521
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
15-hydroxyprostaglandin dehydrogenase (HPGD) OTYZI6JB PGDH_HUMAN Regulation of Drug Effects [9]
Albumin (ALB) OTVMM513 ALBU_HUMAN Drug Response [10]
Bcl-2-like protein 12 (BCL2L12) OTS6IFZY B2L12_HUMAN Gene/Protein Processing [11]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Protein Interaction/Cellular Processes [12]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Gene/Protein Processing [13]
Carnitine O-palmitoyltransferase 1, liver isoform (CPT1A) OTI862QH CPT1A_HUMAN Gene/Protein Processing [12]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [14]
Cytochrome c (CYCS) OTBFALJD CYC_HUMAN Protein Interaction/Cellular Processes [15]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Gene/Protein Processing [16]
Fatty acid-binding protein, brain (FABP7) OTRE2H4G FABP7_HUMAN Drug Response [17]
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 15-Hydroxyprostaglandin dehydrogenase generation of electrophilic lipid signaling mediators from hydroxy -3 fatty acids. J Biol Chem. 2015 Feb 27;290(9):5868-80. doi: 10.1074/jbc.M114.635151. Epub 2015 Jan 12.
10 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.
11 The effect of combination treatment with docosahexaenoic acid and 5-fluorouracil on the mRNA expression of apoptosis-related genes, including the novel gene BCL2L12, in gastric cancer cells. In Vitro Cell Dev Biol Anim. 2009 Jan-Feb;45(1-2):69-74. doi: 10.1007/s11626-008-9154-5. Epub 2008 Nov 18.
12 Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets. DNA Cell Biol. 2004 Aug;23(8):519-26. doi: 10.1089/1044549041562267.
13 Association of serum n-3 polyunsaturated fatty acids with C-reactive protein in men. Eur J Clin Nutr. 2012 Jun;66(6):736-41. doi: 10.1038/ejcn.2011.195. Epub 2011 Nov 23.
14 A novel biologically active acid stable liposomal formulation of docosahexaenoic acid in human breast cancer cell lines. Chem Biol Interact. 2016 May 25;252:1-8. doi: 10.1016/j.cbi.2016.03.035. Epub 2016 Apr 1.
15 Docosahexaenoic acid increases the expression of oxidative stress-induced growth inhibitor 1 through the PI3K/Akt/Nrf2 signaling pathway in breast cancer cells. Food Chem Toxicol. 2017 Oct;108(Pt A):276-288. doi: 10.1016/j.fct.2017.08.010. Epub 2017 Aug 12.
16 The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes. Life Sci. 2006 Nov 25;79(26):2432-40.
17 A fatty acid-binding protein 7/RXR pathway enhances survival and proliferation in triple-negative breast cancer. J Pathol. 2012 Nov;228(3):310-21. doi: 10.1002/path.4001. Epub 2012 Apr 18.