Investigational Drug Details
| Drug ID: | D527 |
| Drug Name: | EPA/DHA |
| Synonyms: | omega-3 fatty acid |
| Type: | Supplement |
| DrugBank ID: | DB11133 |
| DrugBank Description: | Omega-3 fatty acids is an ingredient found in a variety of supplements and vitamins. |
| PubChem ID: | -- |
| CasNo: | 329042-31-1 |
| Repositioning for NAFLD: | No |
| SMILES: | -- |
| InChiKey: | -- |
| Molecular Weight: | -- |
| 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: | -- |
| Therapeutic Category: | -- |
| Clinical Trial Progress: | Clinical trial on-going (JPRN-UMIN000012886) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0634 | JPRN-UMIN000012886 | Not applicable | Not Recruiting | No Results Available | 17/01/2014 | 2 April 2019 | 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 | |
|---|---|---|---|---|---|
| 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 | |
|---|---|---|---|---|
| A00141 | 35212227 | J Agric Food Chem | Targeted Lipidomics Reveal the Effects of Different Phospholipids on the Phospholipid Profiles of Hepatic Mitochondria and Endoplasmic Reticulum in High-Fat/High-Fructose-Diet-Induced Nonalcoholic Fatty Liver Disease Mice. | Details |
| A14574 | 29345914 | J Agric Food Chem | Comparative Analysis of EPA/DHA-PL Forage and Liposomes in Orotic Acid-Induced Nonalcoholic Fatty Liver Rats and Their Related Mechanisms. | Details |
| A20042 | 26193881 | Lipids Health Dis | Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the development of fatty liver in mice. | Details |
| A52946 | 19148125 | Obesity (Silver Spring) | Prevention and reversal of obesity and glucose intolerance in mice by DHA derivatives. | Details |