Repositioning Candidate Details
| Candidate ID: | R0226 |
| Source ID: | DB00636 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Clofibrate |
| Synonyms: | 2-(4-Chlorophenoxy)-2-methylpropanoic acid ethyl ester; 2-(p-Chlorophenoxy)-2-methylpropionic acid ethyl ester; alpha-(p-Chlorophenoxy)isobutyric acid, ethyl ester; alpha-p-Chlorophenoxyisobutyryl ethyl ester; Clofibrate; EPIB; Ethyl 2-(p-chlorophenoxy)isobutyrate; Ethyl chlorophenoxyisobutyrate; Ethyl clofibrate; Liprin |
| Molecular Formula: | C12H15ClO3 |
| SMILES: | CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 |
| Structure: |
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| DrugBank Description: | A fibric acid derivative used in the treatment of hyperlipoproteinemia type III and severe hypertriglyceridemia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986) |
| CAS Number: | 637-07-0 |
| Molecular Weight: | 242.699 |
| DrugBank Indication: | For Primary Dysbetalipoproteinemia (Type III hyperlipidemia) that does not respond adequately to diet. This helps control high cholesterol and high triglyceride levels. |
| DrugBank Pharmacology: | Clofibrate is an antilipidemic agent similar to gemfibrozil. It acts to lower elevated serum lipids by reducing the very low-density lipoprotein fraction (S<sub>f</sub> 20-400) rich in triglycerides. Serum cholesterol may be decreased, particularly in those patients whose cholesterol elevation is due to the presence of IDL as a result of Type III hyperlipoproteinemia. Several investigators have observed in their studies that clofibrate may produce a decrease in cholesterol linoleate but an increase in palmitoleate and oleate, the latter being considered atherogenic in experimental animals. The significance of this finding is unknown at this time. Reduction of triglycerides in some patients treated with clofibrate or certain of its chemically and clinically similar analogs may be associated with an increase in LDL cholesterol. Increase in LDL cholesterol has been observed in patients whose cholesterol is initially normal. Animal studies suggest that clofibrate interrupts cholesterol biosynthesis prior to mevalonate formation. |
| DrugBank MoA: | Clofibrate increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Clofibrate also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL. Also, as a fibrate, Clofibrate is an agonist of the PPAR-α receptor in muscle, liver, and other tissues. This agonism ultimately leads to modification in gene expression resulting in increased beta-oxidation, decreased triglyceride secretion, increased HDL, increased lipoprotein lipase activity. |
| Targets: | Peroxisome proliferator-activated receptor alpha agonist |
| Inclusion Criteria: | Target associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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