| Candidate ID: | R1497 |
| Source ID: | DB13873 |
| Source Type: | approved |
| Compound Type: |
small molecule
|
| Compound Name: |
Fenofibric acid
|
| Synonyms: |
--
|
| Molecular Formula: |
C17H15ClO4
|
| SMILES: |
CC(C)(OC1=CC=C(C=C1)C(=O)C1=CC=C(Cl)C=C1)C(O)=O
|
| Structure: |
|
| DrugBank Description: |
Fenofibric acid is a lipid-lowering agent that is used in severe hypertriglyceridemia, primary hyperlipidemia, and mixed dyslipidemia. It works to decrease elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, apolipoprotein B, while increasing high-density lipoprotein cholesterol. Due to its high hydrophilicity and poor absorption profile, prodrug ,, and other conjugated compounds of fenofibric acid, such as choline fenofibrate, have been developed for improved solubility, gastrointestinal absorption, and bioavailability, and more convenient administration.
|
| CAS Number: |
42017-89-0
|
| Molecular Weight: |
318.75
|
| DrugBank Indication: |
For use as an adjunctive therapy to diet to: (a) reduce triglyceride levels in adult patients with severe hypertriglyceridemia, and (b) reduce elevated total cholesterol, low-density-lipoprotein (LDL-C), triglycerides, and apolipoprotein B, and to increase high-density-lipoprotein (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb).
|
| DrugBank Pharmacology: |
Various clinical studies have shown that elevated levels of total cholesterol, low-desnsity-lipoprotein (LDL-C), and apolipoprotein B (apo B) - an LDL membrane complex - are associated with human atherosclerosis . Concurrently, decreased levels of high-density-lioprotein (HDL-C) and its transport complex, apolipoproteins apo AI and apo AII, are associated with the development of atherosclerosis . Furthermore, epidemiological investigations demonstrate that cardiovascular morbidity and mortality vary directly with the levels of total cholesterol, LDL-C, and triglycerides, and inversely with the level of HDL-C .
Fenofibric acid, the active metabolite of fenofibrate, subsequently produces reductions in total cholesterol, LDL-C, apo B, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients . Moreover, such treatment with fenofibrate also results in increases in HDL-C and apo AI and apo AII .
|
| DrugBank MoA: |
Having performed clinical studies with in vivo transgenic mice and in vitro human hepatocyte cultures, it is believed that the principal mechanism of action of fenofibric acid is demonstrated through its capability to activate peroxisome proliferator receptor alpha (PPAR-alpha) .
By activating PPAR-alpha, fenofibric acid increases lipolysis and the elimination of triglyceride-rich particles from plasma by actuating lipoprotein lipase and reducing production of apoprotein C-III, which acts as an inhibitor of lipoprotein lipase activity . The resultant decrease in triglycerides causes an alteration in the size and composition of low-density-lipoprotein from small, dense particles to large, buoyant ones . The size of these larger low-density-lipoprotein particles have a greater affinity for cholesterol receptors and are therefore catabolized more rapidly . Additionally, fenofibric acid's activation of PPAR-alpha also induces an increase in the synthesis of apoproteins apo A-I, apo A-II, and high-density-lipoprotein .
Moreover, the use of fenofibric acid can also act to reduce serum uric acid levels in ordinary or hyperuricemic individuals by increasing the urinary excretion of uric acid .
|
| Targets: |
Peroxisome proliferator-activated receptor alpha agonist; Matrix metalloproteinase-25 unknown; Peroxisome proliferator-activated receptor gamma; Peroxisome proliferator-activated receptor delta unknown; Nuclear receptor subfamily 1 group I member 2 partial agonist
|
| Inclusion Criteria: |
Target associated
|
