Investigational Drug Details
| Drug ID: | D406 |
| Drug Name: | Gemfibrozil |
| Synonyms: | 2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid; Gemfibrozil |
| Type: | Chemical drug |
| DrugBank ID: | DB01241 |
| DrugBank Description: | Gemfibrozil is a fibric acid agent, similar to , used to treat Type IIb, IV, and V hyperlipidemias. Gemfibrozil is not a first line treatment and is prescribed to patients who have not responded adequately to weight loss, diet, exercise, and other medications. Gemfibrozil was granted FDA approval on 21 December 1981. |
| PubChem ID: | -- |
| CasNo: | 25812-30-0 |
| Repositioning for NAFLD: | Yes |
| SMILES: | CC1=CC(OCCCC(C)(C)C(O)=O)=C(C)C=C1 |
| Structure: |
|
| InChiKey: | HEMJJKBWTPKOJG-UHFFFAOYSA-N |
| Molecular Weight: | 250.3334 |
| DrugBank Targets: | Peroxisome proliferator-activated receptor alpha agonist; Solute carrier organic anion transporter family member 1B1 inhibitor; Solute carrier family 22 member 8 inhibitor; Solute carrier organic anion transporter family member 2B1 inhibitor |
| DrugBank MoA: | Gemfibrozil activates peroxisome proliferator-activated receptor-α (PPARα), which alters lipid metabolism. This activation leads to increased HDL, apo AI, apo AII, lipoprotein lipase (LPL), inhibition of apo B synthesis, peripheral lipolysis, decreased removal of free fatty acids by the liver, and increased clearance of apoB. Upregulated LPL reduces plasma triglyceride levels. Decreased hepatic removal of fatty acids decreases the production of triglycerides. The effects on apoB synthesis and clearance decrease VLDL production which also reduce plasma triglyceride levels. Gemfibrozil's glucuronide metabolite is also an inhibitor of CYP2C8. |
| DrugBank Pharmacology: | Gemfibrozil alters lipid metabolism to treat patients with hyperlipidemia. The duration of action requires twice daily dosing as the mean residence time of gemfibrozil is up to 9.6h in patients with chronic renal failure. Gemfibrozil has a wide therapeutic index as trials with twice the standard dose were not associated with severe side effects. Patients taking gemfibrozil may be at an increased risk of developing cholelithiasis and cholecystitis, as seen in patients taking . |
| DrugBank Indication: | Gemfibrozil is indicated to treat patients with Types IV and V hyperlipidemia who have elevated serum triglycerides (usually above 2000mg/dL), elevated VLDL cholesterol, fasting chylomicrons, are at risk of developing pancreatitis, and do not adequately respond to dietary restrictions. Gemfibrozil is also indicated to reduce the risk of developing coronary heart disease in patients with Type IIb hyperlipidemia without history or symptoms of coronary heart disease; who do not adequately respond to weight loss, diet, exercise, and other medications; and have low HDL, raised LDL, and raised triglycerides. |
| Targets: | PPARA agonist; SLCO1B1 inhibitor; SLC22A8 inhibitor; SLCO2B1 inhibitor; SLCO1B3 inhibitor |
| Therapeutic Category: | Hypolipidemic drug |
| Clinical Trial Progress: | -- |
| Latest Progress: | Under investigation |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T03 | Peroxisome proliferator-activated receptor alpha | PPARA | agonist | Nuclear hormone receptor | Q07869 | PPARA_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 |
| 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 |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A04068 | 33771699 | Pharmacol Res | Epigenetics in NAFLD/NASH: Targets and therapy. | Details |
| A10392 | 31357780 | Zhonghua Gan Zang Bing Za Zhi | [A new attempt with lipoprotein lipase agonists in the treatment of nonalcoholic steatohepatitis]. | Details |
| A11926 | 30680004 | Exp Ther Med | Gemfibrozil reduces lipid accumulation in SMMC-7721 cells via the involvement of PPARα and SREBP1. | Details |
| A12660 | 30341231 | Postgrad Med J | Pharmacological interventions for non-alcoholic fatty liver disease: a systematic review and network meta-analysis. | Details |
| A13821 | 29743187 | Mol Pharmacol | Effects of Farnesoid X Receptor Activation on Arachidonic Acid Metabolism, NF-kB Signaling, and Hepatic Inflammation. | Details |
| A13975 | 29662003 | Int J Mol Sci | PPAR Agonists and Metabolic Syndrome: An Established Role? | Details |
| A17175 | 27930988 | Biomed Pharmacother | Potential involvement of PPAR α activation in diminishing the hepatoprotective effect of fenofibrate in NAFLD: Accuracy of non- invasive panel in determining the stage of liver fibrosis in rats. | Details |
| A27130 | 21180532 | Therap Adv Gastroenterol | Current status of therapy in nonalcoholic Fatty liver disease. | Details |
| A27577 | 17935056 | Diab Vasc Dis Res | The role of fenofibrate in clinical practice. | Details |
| A28416 | 15114291 | Ann Hepatol | Treatment of nonalcoholic fatty liver disease. | Details |
| A28479 | 12739988 | Expert Opin Pharmacother | Current best treatment for non-alcoholic fatty liver disease. | Details |
| A28507 | 12406446 | Best Pract Res Clin Gastroenterol | Treatment of non-alcoholic steatohepatitis. | Details |
| A37543 | 15457967 | Ther Umsch | [Alcoholic and non-alcoholic steatohepatitis]. | Details |
| A40857 | 6572892 | Postgrad Med | Gemfibrozil in combination with other drugs for severe hyperlipidemia. Preliminary study comprising four cases. | Details |
| A46860 | 12408779 | Curr Treat Options Gastroenterol | Therapeutic Options in Nonalcoholic Fatty Liver Disease. | Details |
| A46890 | 11296699 | Semin Liver Dis | Treatment of nonalcoholic fatty liver: present and emerging therapies. | Details |
| A48449 | 10453959 | J Hepatol | A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. | Details |
| A48914 | 24710571 | Arch Toxicol | LC-MS-based metabolomics: an update. | Details |
| A53099 | 14728015 | Am J Cardiovasc Drugs | Drug treatment of combined hyperlipidemia. | Details |