Investigational Drug Details
| Drug ID: | D033 |
| Drug Name: | Bezafibrate |
| Synonyms: | 2-(p-(2-(p-Chlorobenzamido)ethyl)phenoxy)-2-methylpropionic acid; Bezafibrate |
| Type: | Chemical drug |
| DrugBank ID: | DB01393 |
| DrugBank Description: | Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. |
| PubChem ID: | 39042 |
| CasNo: | 41859-67-0 |
| Repositioning for NAFLD: | Yes |
| SMILES: | CC(C(O)=O)(OC1=CC=C(CCNC(C2=CC=C(Cl)C=C2)=O)C=C1)C |
| Structure: |
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| InChiKey: | IIBYAHWJQTYFKB-UHFFFAOYSA-N |
| Molecular Weight: | 361.825 |
| DrugBank Targets: | Peroxisome proliferator-activated receptor alpha agonist; Peroxisome proliferator-activated receptor delta agonist; Peroxisome proliferator-activated receptor gamma agonist; Nuclear receptor subfamily 1 group I member 2 partial agonist; Retinoic acid rece |
| DrugBank MoA: | It is generally accepted that bezafibrate is likely an agonist of PPAR-alpha. However, certain other investigations have also suggested that the substance might also elicit some effects on PPAR-gamma and PPAR-delta too. |
| DrugBank Pharmacology: | Bezafibrate is an antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. Bezafibrate lowers elevated blood lipids (triglycerides and cholesterol). Elevated VLDL and LDL are reduced by treatment with bezafibrate, whilst HDL-levels are increased. The activity of triglyceride lipases (lipoprotein lipase and hepatic lipoproteinlipase) involved in the catabolism of triglyceride-rich lipoproteins is increased by bezafibrate. In the course of the intensified degradation of triglyceride-rich lipoproteins (chylomicrons, VLDL) precursors for the formation of HDL are formed which explains an increase in HDL. Furthermore, cholesterol biosynthesis is reduced by bezafibrate, which is accompanied by a stimulation of the LDL-receptor-mediated lipoprotein catabolism. Elevated fibrinogen appears to be an important risk-factor, alongside the lipids, smoking and hypertension, in the development of atheroma. Fibrinogen plays an important role in viscosity, and therefore blood flow, and also appears to play an important role in thrombus development and lysability. Bezafibrate exerts an effect on thrombogenic factors. A significant decrease in elevated plasma fibrinogen levels can be achieved. This may lead, amongst other things, to a reduction in both blood and plasma viscosity. Inhibition of platelet aggregation has also been observed. A reduction in blood glucose concentration due to an increase in glucose tolerance has been reported in diabetic patients. In the same patients, the concentration of fasting and postprandial free fatty acids was reduced by bezafibrate. |
| DrugBank Indication: | For the treatment of primary hyperlipidaemia types IIa, IIb, III, IV and V (Fredrickson classification) corresponding to groups I, II and III of the European Atherosclerosis Society guidelines - when diet alone or improvements in lifestyle such as increased exercise or weight reduction do not lead to an adequate response. Also for the treatment of secondary hyperlipidaemias, e.g. severe hypertriglyceridemias, when sufficient improvement does not occur after correction of the underlying disorder (e.g. diabetes mellitus). |
| Targets: | PPARA agonist; PPARD agonist; PPARG agonist; NR1I2 partial agonist |
| Therapeutic Category: | Improve insulin resistance; Anti-inflammatory |
| Clinical Trial Progress: | Phase 0 on-going (ChiCTR2000036225) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0547 | JPRN-UMIN000027337 | Not selected | Recruiting | No Results Available | 14/05/2017 | 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 |
| T04 | Peroxisome proliferator-activated receptor delta | PPARD | agonist | Nuclear hormone receptor | Q03181 | PPARD_HUMAN | Details |
| T05 | Peroxisome proliferator-activated receptor gamma | PPARG | agonist | Nuclear hormone receptor | P37231 | PPARG_HUMAN | Details |
| T18 | Acetyl-CoA carboxylase 1 | ACACA | inhibitor | Enzyme | Q13085 | ACACA_HUMAN | Details |
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | 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 | |
|---|---|---|---|---|
| A07125 | 32613381 | Cell Biol Toxicol | Human hepatic in vitro models reveal distinct anti-NASH potencies of PPAR agonists. | Details |
| A10110 | 31480575 | Biomolecules | Raw Bowl Tea (Tuocha) Polyphenol Prevention of Nonalcoholic Fatty Liver Disease by Regulating Intestinal Function in Mice. | Details |
| A10392 | 31357780 | Zhonghua Gan Zang Bing Za Zhi | [A new attempt with lipoprotein lipase agonists in the treatment of nonalcoholic steatohepatitis]. | Details |
| A10804 | 31182918 | Int J Biol Sci | A Comprehensive Study of High Cholesterol Diet-Induced Larval Zebrafish Model: A Short-Time In Vivo Screening Method for Non-Alcoholic Fatty Liver Disease Drugs. | Details |
| A12854 | 30256948 | Hum Mol Genet | Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia. | Details |
| A16638 | 28271032 | Mol Metab | Bezafibrate ameliorates diabetes via reduced steatosis and improved hepatic insulin sensitivity in diabetic TallyHo mice. | Details |
| A20763 | 25748419 | Life Sci | Singular effects of PPAR agonists on nonalcoholic fatty liver disease of diet-induced obese mice. | Details |
| A21472 | 25296088 | Arq Gastroenterol | Ginseng, green tea or fibrate: valid options for nonalcoholic steatohepatitis prevention? | Details |
| A21897 | 24975050 | Basic Clin Pharmacol Toxicol | Effects of antihypertensive and triglyceride-lowering agents on hepatic copper concentrations in rats with fatty liver disease. | Details |
| A22471 | 24534255 | Toxicol Appl Pharmacol | PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells. | Details |
| A23726 | 23531105 | Lipids Health Dis | Rosiglitazone and bezafibrate modulate gene expression in a rat model of non-alcoholic fatty liver disease--a historical prospective. | Details |
| A23776 | 23489555 | Basic Clin Pharmacol Toxicol | Effects of antihypertensive and triglyceride lowering agents on splenocyte apoptosis in rats with fatty liver. | Details |
| A25342 | 21946918 | Mol Med Rep | Nifedipine prevents hepatic fibrosis in a non-alcoholic steatohepatitis model induced by an L-methionine-and choline-deficient diet. | Details |
| A25682 | 21549692 | Eur J Pharmacol | Effects of bezafibrate in nonalcoholic steatohepatitis model mice with monosodium glutamate-induced metabolic syndrome. | Details |
| A26654 | 20040336 | Int J Clin Pharmacol Ther | Therapeutic effect of bezafibrate against biliary damage: a study of phospholipid secretion via the PPARalpha-MDR3 pathway. | Details |
| A28279 | 15824194 | Hypertension | Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. | Details |
| A28458 | 14598660 | Ryumachi | [Systemic lupus erythematosus with steroid induced non-alcoholic steatohepatitis: a case report]. | Details |
| A28473 | 12883726 | Oncol Rep | Follow-up CT findings of tamoxifen-induced non-alcoholic steatohepatitis (NASH) of breast cancer patients treated with bezafibrate. | Details |
| A36291 | 18513333 | Hepatol Res | Bezafibrate prevents hepatic stellate cell activation and fibrogenesis in a murine steatohepatitis model, and suppresses fibrogenic response induced by transforming growth factor-beta1 in a cultured stellate cell line. | Details |
| A37053 | 16574099 | Eur J Pharmacol | Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet. | Details |