Investigational Drug Details
| Drug ID: | D105 |
| Drug Name: | DHA |
| Synonyms: | (4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid; 22:6-4, 7,10,13,16,19; 22:6(n-3); 4,7,10,13,16,19-docosahexaenoic acid; all-cis-4,7,10,13,16,19-docosahexaenoic acid; all-cis-DHA; cervonic acid; DHA; Doconexent; docosa-4,7,10,13,16,19-hexaenoic acid; Docosahexaenoic acid |
| Type: | Chemical drug |
| DrugBank ID: | DB03756 |
| DrugBank Description: | A mixture of fish oil and primrose oil, doconexent is used as a high-docosahexaenoic acid (DHA) supplement. DHA is a 22 carbon chain with 6 cis double bonds with anti-inflammatory effects. It can be biosythesized from alpha-linolenic acid or commercially manufactured from microalgae. It is an omega-3 fatty acid and primary structural component of the human brain, cerebral cortex, skin, and retina thus plays an important role in their development and function. The amino-phospholipid DHA is found at a high concentration across several brain subcellular fractions, including nerve terminals, microsomes, synaptic vesicles, and synaptosomal plasma membranes . |
| PubChem ID: | 15608515 |
| CasNo: | 6217-54-5 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C(=C\C/C=C\CCC(=O)O)\C/C=C\C/C=C\C/C=C\C/C=C\CC |
| Structure: |
|
| InChiKey: | MBMBGCFOFBJSGT-KUBAVDMBSA-N |
| Molecular Weight: | 328.496 |
| DrugBank Targets: | Peroxisome proliferator-activated receptor alpha ligand; Peroxisome proliferator-activated receptor gamma ligand; Retinoic acid receptor RXR-alpha activator; Retinoic acid receptor RXR-beta activator; Retinoic acid receptor RXR-gamma activator; Sterol reg |
| DrugBank MoA: | DHA and its conversion to other lipid signalling moleccules compete with the arachidonic acid cascade from endogenous phospholipids and shift the inflammatory state to being more anti-inflammatory. DHA inhibits endotoxin-stimulated production of IL-6 and IL-8 in human endothelial cells. Derivatives of DHA are anti-inflammatory lipid mediators. Lipid mediators resolvin D1 and protectin D1 all inhibit transendothelial migration of neutrophils, so preventing neutrophilic infiltration at sites of inflammation, resolvin D1 inhibits IL-1β production, and protectin D1 inhibits TNF and IL-1β production . Monoxydroxy derivative of DHA converted by LOX inhibit thromboxane-induced platelet aggregation. DHA supplementation has also shown to reduce the levels of serum C-reactive protein (CRP) and other circulating markers of inflammation such as neutrophils in hypertriglyceridemic men . DHA acts as a ligand at peroxisome proliferator-activated receptor (PPAR) gamma and alpha that regulate lipid signalling molecule-mediated transduction pathways and modulate inflammation. As a natural ligand, DHA induces a protective effect in retinal tissues by activating retinoid x receptors and subsequent ERK/MAPK signaling pathway in photoreceptors to promote their survival and differentiation, stimulating the expression of antiapoptotic proteins such as Bcl-2 and preserving mitochondrial membrane potential . |
| DrugBank Pharmacology: | DHA in the central nervous system is found in the phospholipid bilayers where it modulates the physical environment and increase the free volume within the membrane bilayer. It influences the G-protein coupled receptor activity and affects transmembrane transport and cell interaction with the exterior world. It is also reported to promote apoptosis, neuronal differentiation and ion channel activity. Like other polyunsaturated fatty acids, DHA acts as a ligand at PPARs that plays an anti-inflammatory effect and regulate inflammatory gene expression and NFκB activation. DHA also gives rise to resolvins and related compounds (e.g., protectins) through pathways involving cyclooxygenase and lipoxygenase enzymes to resolve the inflammatory responses. |
| DrugBank Indication: | Used as a high-docosahexaenoic acid (DHA) oral supplement. |
| Targets: | PPARA ligand; PPARG ligand |
| Therapeutic Category: | Anti-inflammatory |
| Clinical Trial Progress: | Phase 1&2 completed (NCT00885313: DHA supplementation improves liver steatosis and insulin sensitivity in children with NAFLD.) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0314 | NCT01934777 | Phase 3 | Completed | No Results Available | October 2013 | January 14, 2016 | Details |
| L0321 | NCT02098317 | Phase 3 | Completed | No Results Available | January 2014 | January 14, 2016 | Details |
| L0634 | JPRN-UMIN000012886 | Not applicable | Not Recruiting | No Results Available | 17/01/2014 | 2 April 2019 | Details |
| L0655 | EUCTR2012-001975-36-IT | Not applicable | Authorised | No Results Available | 14/06/2012 | 7 January 2013 | Details |
| L0723 | NCT04198805 | Phase 2 | Recruiting | No Results Available | 30/10/2019 | 24 January 2022 | Details |
| L0802 | CTRI/2017/12/010997 | Phase 1 | Not Recruiting | No Results Available | 27/12/2017 | 24 November 2021 | Details |
| L0811 | SLCTR/2017/033 | Not applicable | Not Recruiting | No Results Available | 28/09/2017 | 7 February 2022 | Details |
| L0813 | RBR-8dp876 | Not applicable | Not Recruiting | No Results Available | 19/09/2017 | 7 February 2022 | Details |
| L0839 | IRCT2016082429508N1 | Phase 2 | Not Recruiting | No Results Available | 20/09/2016 | 22 February 2018 | Details |
| L0913 | IRCT2013052313427N1 | Not applicable | Not Recruiting | No Results Available | 22/09/2013 | 22 February 2018 | Details |
| L0968 | NCT00885313 | Phase 1/Phase 2 | Not recruiting | No Results Available | 20/04/2009 | 19 February 2015 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T08 | Tumor necrosis factor | TNF | inhibitor | Cytokine | P01375 | TNFA_HUMAN | Details |
| 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 |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 | |
|---|---|---|---|---|
| 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 |
| A00187 | 35193889 | BMJ Open Gastroenterol | Non-alcoholic fatty liver disease (NAFLD): a significant predictor of gestational diabetes mellitus (GDM) and early pregnancy miscarriages-prospective study in Rajarata Pregnancy Cohort (RaPCo). | Details |
| A00478 | 35067753 | Eur J Nutr | The effects of fish oil plus vitamin D3 intervention on non-alcoholic fatty liver disease: a randomized controlled trial. | Details |
| A00524 | 35053404 | Cells | Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver. | Details |
| A00604 | 35033554 | Eur J Pharmacol | Ursodesoxycholic acid is an FFA4 agonist and reduces hepatic steatosis via FFA4 signaling. | Details |
| A00760 | 34977519 | JHEP Rep | Pegbelfermin selectively reduces secondary bile acid concentrations in patients with non-alcoholic steatohepatitis. | Details |
| A00946 | 34922604 | Trials | Omega-3 mechanism of action in inflammation and endoplasmic reticulum stress in mononuclear cells from overweight non-alcoholic fatty liver disease participants: study protocol for the "Brazilian Omega Study" (BROS)-a randomized controlled trial. | Details |
| A01257 | 34813379 | Metab Syndr Relat Disord | The Myristic Acid:Docosahexaenoic Acid Ratio Versus the n-6 Polyunsaturated Fatty Acid:n-3 Polyunsaturated Fatty Acid Ratio as Nonalcoholic Fatty Liver Disease Biomarkers. | Details |
| A01687 | 34653759 | Biomed Pharmacother | Effects of DHA dietary intervention on hepatic lipid metabolism in apolipoprotein E-deficient and C57BL/6J wild-type mice. | Details |
| A01785 | 34618982 | FASEB J | Omega-3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non-alcoholic fatty liver disease. | Details |
| A02106 | 34505434 | Se Pu | [Identification of LAMTOR1-regulated metabolites using ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry in malignant transformation of liver inflammation]. | Details |
| A02296 | 34433051 | Cell Rep | Epigenomic and transcriptional profiling identifies impaired glyoxylate detoxification in NAFLD as a risk factor for hyperoxaluria. | Details |
| A02899 | 34202667 | Biomolecules | The Role of Resolvins, Protectins and Marensins in Non-Alcoholic Fatty Liver Disease (NAFLD). | Details |
| A02927 | 34195217 | Front Nutr | Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation. | Details |
| A03148 | 34113260 | Front Physiol | Effect of ω-3 Polyunsaturated Fatty Acids-Derived Bioactive Lipids on Metabolic Disorders. | Details |
| A03508 | 33977946 | Food Funct | DHA-enriched phosphatidylserine ameliorates non-alcoholic fatty liver disease and intestinal dysbacteriosis in mice induced by a high-fat diet. | Details |
| A04306 | 33671567 | Cells | Identification of Accessible Hepatic Gene Signatures for Interindividual Variations in Nutrigenomic Response to Dietary Supplementation of Omega-3 Fatty Acids. | Details |
| A04314 | 33668222 | Int J Environ Res Public Health | Tobacco Smoke and CYP1A2 Activity in a US Population with Normal Liver Enzyme Levels. | Details |
| A04548 | 33582286 | Biochim Biophys Acta Mol Cell Biol Lipids | Chronic systemic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver. | Details |
| A04584 | 33572810 | Nutrients | Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity. | Details |