Investigational Drug Details
| Drug ID: | D133 |
| Drug Name: | Fenofibrate |
| Synonyms: | 2-(4-(4-Chlorobenzoyl)phenoxy)-2-methylpropanoic acid 1-methylethyl ester; Fenofibrate; Finofibrate; FNF; Isopropyl (4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl)propionate; Isopropyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionate; Procetofen |
| Type: | Chemical drug |
| DrugBank ID: | DB01039 |
| DrugBank Description: | Fenofibrate is a fibric acid derivative like and . Fenofibrate is used to treat primary hypercholesterolemia, mixed dyslipidemia, severe hypertriglyceridemia. Fenofibrate was granted FDA approval on 31 December 1993. |
| PubChem ID: | 3339 |
| CasNo: | 49562-28-9 |
| Repositioning for NAFLD: | Yes |
| SMILES: | CC(OC(C(C)(OC1=CC=C(C(C2=CC=C(Cl)C=C2)=O)C=C1)C)=O)C |
| Structure: |
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| InChiKey: | YMTINGFKWWXKFG-UHFFFAOYSA-N |
| Molecular Weight: | 360.837 |
| DrugBank Targets: | Peroxisome proliferator-activated receptor alpha agonist; Matrix metalloproteinase-25 inhibitor; Nuclear receptor subfamily 1 group I member 2 partial agonist |
| DrugBank MoA: | Fenofibrate activates peroxisome proliferator activated receptor alpha (PPARα), increasing lipolysis, activating lipoprotein lipase, and reducing apoprotein C-III. PPARα is a nuclear receptor and its activation alters lipid, glucose, and amino acid homeostasis. Activation of PPARα activates transcription of gene transcription and translation that generates peroxisomes filled with hydrogen peroxide, reactive oxygen species, and hydroxyl radicals that also participate in lipolysis. This mechanism of increased lipid metabolism is also associated with increased oxidative stress on the liver. In rare cases this stress can lead to cirrhosis and chronic active hepatitis. |
| DrugBank Pharmacology: | Fenofibrate is a fibrate that activates peroxisome proliferator activated receptor alpha (PPARα) to alter lipid metabolism and treat primary hypercholesterolemia, mixed dyslipidemia, and severe hypertriglyceridemia. Fenofibrate requires once daily dosing and has a half life of 19-27 hours so its duration of action is long. Fenofibrate capsules are given at a dose of 50-150mg daily so the therapeutic index is wide. Patients should be counselled about the risk of rhabdomyolysis, myopathy, and cholelithiasis when taking fibrates. |
| DrugBank Indication: | Fenofibrate is indicated as adjunctive therapy to diet to reduce elevated LDL-C, Total-C, Triglycerides, and Apo B, and to increase HDL-C adults with primary hypercholesterolemia or mixed dyslipidemia. Fenofibrate is also indicated to treat adults with severe hypertriglyceridemia. |
| Targets: | PPARA agonist; NR1I2 partial agonist |
| Therapeutic Category: | Anti-inflammatory |
| Clinical Trial Progress: | Phase 2 completed (NCT02354976: OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism.) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0013 | NCT00262964 | Not applicable | Completed | Has Results | October 2004 | July 11, 2018 | Details |
| L0101 | NCT01289639 | Not applicable | Terminated | Has Results | October 2005 | August 17, 2017 | Details |
| L0109 | NCT00252499 | Not applicable | Terminated | Has Results | October 2005 | August 20, 2014 | Details |
| L0146 | NCT02354976 | Phase 2 | Completed | Has Results | September 1, 2015 | September 25, 2018 | Details |
| L0311 | NCT02891408 | Phase 1 | Completed | Has Results | September 23, 2016 | December 17, 2020 | Details |
| L0401 | JPRN-jRCTs031200280 | Phase 2 | Recruiting | No Results Available | 28/12/2020 | 17 May 2021 | Details |
| L0578 | IRCT2015120819554N10 | Phase 3 | Not Recruiting | No Results Available | 12/07/2016 | 22 February 2018 | Details |
| L0885 | EUCTR2014-003637-26-SE | Phase 2 | Not Recruiting | No Results Available | 23/01/2015 | 22 May 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 |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 | |
|---|---|---|---|---|
| A00348 | 35126113 | Front Pharmacol | Fenofibrate Improves Insulin Resistance and Hepatic Steatosis and Regulates the Let-7/SERCA2b Axis in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice. | Details |
| A00595 | 35035496 | Evid Based Complement Alternat Med | Lanzhang Granules Ameliorate Nonalcoholic Fatty Liver Disease by Regulating the PPARα Signaling Pathway. | Details |
| A00725 | 34988225 | Biomed Res Int | Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis. | Details |
| A00796 | 34964438 | Elife | Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA. | 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 |
| A01843 | 34593018 | BMC Pharmacol Toxicol | Saroglitazar improved hepatic steatosis and fibrosis by modulating inflammatory cytokines and adiponectin in an animal model of non-alcoholic steatohepatitis. | Details |
| A01877 | 34576091 | Int J Mol Sci | Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose. | Details |
| A02352 | 34406209 | Braz J Med Biol Res | α,β-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism. | Details |
| A02426 | 34374658 | J Physiol Pharmacol | Hesperidin, a novel candidate for the successful treatment of high fat diet plus ethanol-induced fatty liver disease in mice. | Details |
| A02682 | 34285335 | Exp Mol Med | Loss of Acot12 contributes to NAFLD independent of lipolysis of adipose tissue. | Details |
| A03107 | 34128328 | Chem Biodivers | Effect of Compounds from Moringa oleifera Lam. on in Vitro Non-Alcoholic Fatty Liver Disease (NAFLD) Model System. | Details |
| A03200 | 34092291 | Chin J Nat Med | Silybin alleviates hepatic lipid accumulation in methionine-choline deficient diet-induced nonalcoholic fatty liver disease in mice via peroxisome proliferator-activated receptor α. | Details |
| A03492 | 33984335 | Metabolism | Fenofibrate, a PPARα agonist, reduces hepatic fat accumulation through the upregulation of TFEB-mediated lipophagy. | Details |
| A06708 | 32774420 | Evid Based Complement Alternat Med | Anti-inflammatory Mechanism of Ruzu Bitters on Diet-Induced Nonalcoholic Fatty Liver Disease in Male Wistar Rats. | Details |
| A06759 | 32757283 | Fundam Clin Pharmacol | Protective effect of fenofibrate against high-fat-high-fructose diet induced non-obese NAFLD in rats. | Details |
| A07125 | 32613381 | Cell Biol Toxicol | Human hepatic in vitro models reveal distinct anti-NASH potencies of PPAR agonists. | Details |
| A07769 | 32360434 | J Hepatol | Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages☆. | Details |
| A07793 | 32353385 | Toxicol Appl Pharmacol | Metabolomic-based assessment reveals dysregulation of lipid profiles in human liver cells exposed to environmental obesogens. | Details |
| A07807 | 32350271 | Nat Commun | Partial impairment of insulin receptor expression mimics fasting to prevent diet-induced fatty liver disease. | Details |
| A08125 | 32239031 | Chem Commun (Camb) | Simultaneous co-assembly of fenofibrate and ketoprofen peptide for the dual-targeted treatment of nonalcoholic fatty liver disease (NAFLD). | Details |