| Candidate ID: | R0527 |
| Source ID: | DB13873 |
| Source Type: | approved |
| Compound Type: |
small molecule
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| Compound Name: |
Fenofibric acid
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| Synonyms: |
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| Molecular Formula: |
C17H15ClO4
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| SMILES: |
CC(C)(OC1=CC=C(C=C1)C(=O)C1=CC=C(Cl)C=C1)C(O)=O
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| Structure: |
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| DrugBank Description: |
Fenofibrate is a third generation fibric acid derivative that is predominantly administered as monotherapy to decrease elevated low-density lipoprotein cholesterol, total cholesterol, triglycerides, apolipoprotein B and alternatively to increase high-density lipoprotein cholesterol in patients diagnosed with primary hyperlipidemia or mixed dyslipidemia and to reduce triglycerides in patients with severe hypertriglyceridemia [FDA Label, A32038]. Fenofibrate however is generally extremely lipophilic, largely insoluble in water, and poorly absorbed [A32038]. As the primary active metabolite of fenofibrate however, various hydrophilic salt formulations of fenofibric acid have since been developed, resulting in therapeutic agents that demonstrate far greater solubility, absorption throughout the gastrointestinal tract, bioavailability, and capability to be administered irrespective of patient food intake [FDA Label, A32038].
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| CAS Number: |
42017-89-0
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| Molecular Weight: |
318.75
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| 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). [FDA Label]
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| 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 [FDA Label]. 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 [FDA Label]. 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 [FDA Label].
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 [FDA Label]. Moreover, such treatment with fenofibrate also results in increases in HDL-C and apo AI and apo AII [FDA Label].
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| 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) [FDA Label].
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 [FDA Label]. 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 [FDA Label]. The size of these larger low-density-lipoprotein particles have a greater affinity for cholesterol receptors and are therefore catabolized more rapidly [FDA Label]. 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 [FDA Label].
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 [FDA Label].
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| Targets: |
Peroxisome proliferator-activated receptor alpha; Matrix metalloproteinase-25; Peroxisome proliferator-activated receptor gamma; Peroxisome proliferator-activated receptor delta; Nuclear receptor subfamily 1 group I member 2
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| Inclusion Criteria: |
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