Investigational Drug Details
| Drug ID: | D125 |
| Drug Name: | Epanova |
| Synonyms: | n-3 fatty acids; Omega 3 fatty acids; Omega-3; Omega-3 acid; Omega-3 acid triglycerides; Omega-3 fatty acid; Omega-3 phospholipids; Omega-3 polyunsaturated fatty acids; Omega-3 polyunsaturates; Omega-3-acid triglycerides; Phospholipids; ω-3 fatty acids |
| Type: | Chemical drug |
| DrugBank ID: | DB11133 |
| DrugBank Description: | Omega-3 fatty acids are polyunsaturated fatty acids (PUFAs) with a double bond at the third carbon atom from the end of the carbon chain. The three types of omega-3 fatty acids involved in human physiology are α-linolenic acid (ALA) (found in plant oils), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) (both commonly found in fish oil that originally come from microalgae that is further consumed by phytoplankton, a source of diet for fish). Omega-3 fatty acids play a critical role in metabolism and cellular function and they are available as daily supplements. On September 8, 2004, the U.S. Food and Drug Administration gave "qualified health claim" status to EPA and DHA omega-3 fatty acids. Therapeutic products containing omega-3 fatty acid and its derivatives for treatment of hypertriglyceridemia include Lovaza, Omtryg, Epanova, and Vascepa. |
| PubChem ID: | 56842239 |
| CasNo: | 329042-31-1 |
| Repositioning for NAFLD: | Yes |
| SMILES: | OC(=O)CCCCCCC/C=C\C/C=C\C/C=C\CC.OC(=O)CCC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CC.OC(=O)CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CC |
| Structure: |
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| InChiKey: | QPEOIOLHJXXJFN-GNGJDXFDSA-N |
| Molecular Weight: | 909.39 |
| DrugBank Targets: | Peroxisome proliferator-activated receptor gamma ligand; Peroxisome proliferator-activated receptor alpha activator; Sterol regulatory element-binding protein 1 inhibitor |
| DrugBank MoA: | Omega-3 fatty acids mediate anti-inflammatory effects and increased levels of EPA or DHA has shown to decrease the levels of PGE2 and 4 series-LT. Eicosapentaenoic acids compete with constitutive levels of arachidonic acid in cell membranes for the same desaturation enzymes and produce 3-series prostaglandins and thromboxanes, and 5-series leukotrienes which have low pro-inflammatory potential. The alteration in leukotriene biosynthesis due to higher concentration of omega-3 fatty acids compared to arachidonic acid underlies the anti-inflammatory effects. EPA and DHA also give rise to resolvins and related lipid signalling molecules such as protectins via cyclooxygenase and lipoxygenase pathways, which have anti-inflammatory effects. They inhibit transendothelial migration of neutrophils and inhibit TNF and IL-1β production. Omega-3 fatty acids also decrease adhesion molecule expression on leukocytes and on endothelial cells and decrease intercellular adhesive interactions. Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator-activated receptor (PPAR) gamma that regulates inflammatory gene expression and NFκB activation. PPAR alpha activation is also associated with induction of COX-2 expression. The role of EPA and DHA in reducing triglyceride levels include inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase, increased mitochondrial and peroxisomal-beta-oxidation in the liver, decreased lipogenesis in the liver, and increased plasma lipoprotein lipase activity. They also may reduce triglyceride synthesis because they are poor substrates for the enzymes responsible for TG synthesis, and EPA and DHA inhibit esterification of other fatty acids. |
| DrugBank Pharmacology: | Omega-3 fatty acids are triglycerides that get broken down into smaller fatty acid units. They act to reduce plasma triglyceride levels however increase the cholesterol levels and are thought to possess potent antiarrythmic effects. Polyunsaturated fatty acids including eicosapentaenoic and docosahexaenoic acid mediate important cellular function such as inhibition of platelet function, prolongation of bleeding time, anti-inflammatory effects and reduction of plasma fibrinogen. Polyunsaturated fatty acids are components of the phospholipids that form the structures of the cell membranes and also serve as energy source. They form eicosanoids which are important signalling molecules with wide-ranging functions in the body's cardiovascular, pulmonary, immune and endocrine systems. DHA tends to exist in high concentrations in the retina, brain (via uptake by Mfsd2a as a transporter), and sperm. |
| DrugBank Indication: | Provided as daily supplements. Aa preparation of omega-3-acid ethyl esters is licensed in UK for prevention of recurrent events after myocardial infarction in addition to treatment of hypertriglyceridaemia. |
| Targets: | PPARG ligand; PPARA activator |
| Therapeutic Category: | Enhance lipid metabolism |
| Clinical Trial Progress: | Clinical trial completed (NCT04281121) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0146 | NCT02354976 | Phase 2 | Completed | Has Results | September 1, 2015 | September 25, 2018 | Details |
| L0305 | NCT04481594 | Phase 1 | Recruiting | No Results Available | September 8, 2020 | February 10, 2021 | Details |
| L0623 | EUCTR2014-003638-26-SE | Not applicable | Not Recruiting | No Results Available | 03/10/2014 | 11 April 2016 | Details |
| L0885 | EUCTR2014-003637-26-SE | Phase 2 | Not Recruiting | No Results Available | 23/01/2015 | 22 May 2017 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Peroxisome proliferator-activated receptor alpha | PPARA | agonist | Nuclear hormone receptor | Q07869 | PPARA_HUMAN | Details |
| T05 | Peroxisome proliferator-activated receptor gamma | PPARG | agonist | Nuclear hormone receptor | P37231 | PPARG_HUMAN | Details |
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| T21 | Diacylglycerol O-acyltransferase 2 | DGAT2 | inhibitor | Enzyme | Q96PD7 | DGAT2_HUMAN | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Article ID | PMID | Source | Title |
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