Investigational Drug Details
| Drug ID: | D075 |
| Drug Name: | Choline |
| Synonyms: | Bilineurine; Choline ion; N-trimethylethanolamine; N,N,N-trimethylethanol-ammonium; trimethylethanolamine; Vitamin J |
| Type: | Supplement |
| DrugBank ID: | DB00122 |
| DrugBank Description: | A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. |
| PubChem ID: | 305 |
| CasNo: | 62-49-7 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C([N+](C)(C)C)CO |
| Structure: |
|
| InChiKey: | OEYIOHPDSNJKLS-UHFFFAOYSA-N |
| Molecular Weight: | 104.173 |
| DrugBank Targets: | Choline-phosphate cytidylyltransferase B product of; Acetylcholinesterase product of; Choline-phosphate cytidylyltransferase A product of; Phospholipase D2 product of; Cholinesterase product of; Phospholipase D1 product of; Phosphoethanolamine/phosphochol |
| DrugBank MoA: | Choline is a major part of the polar head group of phosphatidylcholine. Phosphatidylcholine's role in the maintenance of cell membrane integrity is vital to all of the basic biological processes: information flow, intracellular communication and bioenergetics. Inadequate choline intake would negatively affect all these processes. Choline is also a major part of another membrane phospholipid, sphingomyelin, also important for the maintenance of cell structure and function. It is noteworthy and not surprising that choline deficiency in cell culture causes apoptosis or programmed cell death. This appears to be due to abnormalities in cell membrane phosphatidylcholine content and an increase in ceramide, a precursor, as well as a metabolite, of sphingomyelin. Ceramide accumulation, which is caused by choline deficiency, appears to activate Caspase, a type of enzyme that mediates apoptosis. Betaine or trimethylglycine is derived from choline via an oxidation reaction. Betaine is one of the factors that maintains low levels of homocysteine by resynthesizing L-methionine from homocysteine. Elevated homocysteine levels are a significant risk factor for atherosclerosis, as well as other cardiovascular and neurological disorders. Acetylcholine is one of the major neurotransmitters and requires choline for its synthesis. Adequate acetylcholine levels in the brain are believed to be protective against certain types of dementia, including Alzheimer's disease. |
| DrugBank Pharmacology: | This compound is needed for good nerve conduction throughout the CNS (central nervous system) as it is a precursor to acetylcholine (ACh). Choline is also needed for gallbladder regulation, liver function and lecithin (a key lipid) formation. Choline also aids in fat and cholesterol metabolism and prevents excessive fat build up in the liver. Choline has been used to mitigate the effects of Parkinsonism and tardive dyskinesia. Choline deficiencies may result in excessive build-up of fat in the liver, high blood pressure, gastric ulcers, kidney and liver dysfunction and stunted growth. |
| DrugBank Indication: | For nutritional supplementation, also for treating dietary shortage or imbalance |
| Targets: | PLD2 product of; PLD1 product of |
| Therapeutic Category: | -- |
| Clinical Trial Progress: | Phase 2 on-going (JPRN-UMIN000006192) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0033 | NCT04109742 | Phase 2 | Withdrawn | No Results Available | December 9, 2019 | September 27, 2021 | Details |
| L0155 | NCT01807910 | Early Phase 1 | Withdrawn | No Results Available | October 2013 | October 23, 2013 | Details |
| L0314 | NCT01934777 | Phase 3 | Completed | No Results Available | October 2013 | January 14, 2016 | Details |
| L0415 | ChiCTR2000036882 | Phase 1 | Recruiting | No Results Available | 25/08/2020 | 21 September 2020 | Details |
| L0478 | JPRN-jRCTs031180159 | Not applicable | Not Recruiting | Has Results | 26/02/2019 | 10 January 2022 | Details |
| L0517 | JPRN-UMIN000030355 | Not applicable | Recruiting | No Results Available | 15/12/2017 | 17 May 2021 | Details |
| L0533 | NCT01056133 | Phase 2 | Not recruiting | No Results Available | 22/01/2010 | 23 May 2016 | Details |
| L0565 | ChiCTR-IOR-16009599 | Other | Not Recruiting | No Results Available | 25/10/2016 | 18 April 2017 | Details |
| L0666 | JPRN-UMIN000006192 | Phase 2 | Not Recruiting | No Results Available | 18/08/2011 | 2 April 2019 | Details |
| L0700 | NCT04411862 | Phase 3 | Not recruiting | No Results Available | 10/05/2020 | 12 December 2020 | Details |
| L0754 | CTRI/2019/04/018550 | Not applicable | Not Recruiting | No Results Available | 10/04/2019 | 24 November 2021 | Details |
| L0910 | ISRCTN33414972 | Not applicable | Not Recruiting | No Results Available | 16/12/2013 | 27 February 2017 | 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 |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00040 | 35247631 | Cell Mol Gastroenterol Hepatol | The critical and diverse roles of CD4-CD8- double negative T cells in nonalcoholic fatty liver disease. | Details |
| A00049 | 35243280 | JHEP Rep | Cellular origins of regenerating liver and hepatocellular carcinoma. | Details |
| A00056 | 35240344 | Cell Mol Gastroenterol Hepatol | Activation of Liver mTORC1 Protects Against NASH via Dual Regulation of VLDL-TAG Secretion and De Novo Lipogenesis. | Details |
| A00069 | 35232986 | Sci Rep | Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation. | Details |
| A00100 | 35220131 | Phytomedicine | 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside ameliorates NAFLD via attenuating hepatic steatosis through inhibiting mitochondrial dysfunction dependent on SIRT5. | Details |
| A00122 | 35213001 | Methods Mol Biol | In Vivo Analysis of Necrosis and Ferroptosis in Nonalcoholic Steatohepatitis (NASH). | Details |
| 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 |
| A00142 | 35212074 | J Magn Reson Imaging | Water Specific MRI T1 Mapping for Evaluating Liver Inflammation Activity Grades in Rats With Methionine-Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease. | Details |
| A00158 | 35204522 | Diagnostics (Basel) | A Comparative Study of the Triglycerides/HDL Ratio and Pseudocholinesterase Levels in Patients with Bladder Cancer. | Details |
| A00209 | 35185113 | J Pediatr Gastroenterol Nutr | Comparison of the Lipidomic Signature of Fatty Liver in Children and Adults: A Cross-Sectional Study. | Details |
| A00221 | 35178496 | APL Bioeng | Development of resveratrol with thiolated alginate as a supplement to prevent nonalcoholic fatty liver disease (NAFLD). | Details |
| A00229 | 35174500 | J Sci Food Agric | Identification of a novel probiotic and its protective effects on NAFLD via modulating gut microbial community. | Details |
| A00253 | 35164140 | Molecules | A Comparison of the Gene Expression Profiles of Non-Alcoholic Fatty Liver Disease between Animal Models of a High-Fat Diet and Methionine-Choline-Deficient Diet. | Details |
| A00257 | 35163821 | Int J Mol Sci | Proglumide Reverses Nonalcoholic Steatohepatitis by Interaction with the Farnesoid X Receptor and Altering the Microbiome. | Details |
| A00294 | 35148334 | PLoS One | Procollagen C-Proteinase Enhancer-1 (PCPE-1) deficiency in mice reduces liver fibrosis but not NASH progression. | Details |
| A00395 | 35102146 | Nat Commun | Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis. | Details |
| A00414 | 35093339 | Life Sci | Endothelial group IVA phospholipase A2 promotes hepatic fibrosis with sinusoidal capillarization in the early stage of non-alcoholic steatohepatitis in mice. | Details |
| A00456 | 35075477 | Lab Med | Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry. | Details |
| A00457 | 35075185 | Sci Rep | MAFLD progression contributes to altered thalamus metabolism and brain structure. | Details |
| A00485 | 35065166 | Life Sci | Hepatocellular BChE as a therapeutic target to ameliorate hypercholesterolemia through PRMT5 selective degradation to restore LDL receptor transcription. | Details |