| CAS |
No.49562-28-9 |
| 中文名称 |
非诺贝特(10mM in DMSO,无菌） |
| 英文名称 |
Fenofibrate(10mM in DMSO，Sterile） |
| 分子式 |
C20H21ClO4 |
| 分子量 |
360.83 |
| 溶解性 |
请根据自己的实验要求使用。 |
| 外观(性状) |
无菌溶液 |
| 储存条件 |
Stroe at -20℃，6 months. |
| 靶点 |
PPAR;Cytochrome P450 |
| 通路 |
Cell Cycle;DNA Damage/DNA Repair;Metabolic Enzyme&Protease;Apoptosis |
| 背景说明 |
Fenofibrate是一种选择性的PPARα激动剂。Fenofibrate抑制细胞色素 P450 亚型，例如CYP2C19，CYP2B6，CYP2C9，CYP2C8 和 CYP3A4。 |
| 生物活性 |
Fenofibrate is a selective PPARα agonist with an EC50 of 30 μM. Fenofibrate also inhibits human cytochrome P450 isoforms， with IC50s of 0.2， 0.7， 9.7， 4.8 and 142.1 μM for CYP2C19， CYP2B6， CYP2C9， CYP2C8， and CYP3A4， respectively.[1-2] |
| In Vitro |
Fenofibrate is a relatively potent inhibitor of CYP2B6 (IC50=0.7±0.2 μM) and CYP2C19 (IC50=0.2±0.1 μM). Fenofibrate is also a moderate inhibitor of CYP2C8 (IC50=4.8±1.7 μM) and CYP2C9 (IC50=9.7 μM)[1]. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. Fenofibrate is a well-known PPARα agonist， but an in vitro assessment of 209 frequently prescribed drugs and related xenobiotics suggests that Fenofibrate is also a potent inhibitor of cytochrome P450 epoxygenase (CYP)2C. The affinity of Fenofibrate to CYP2C is >10 times higher (EC50=2.39±0.4 μM) than to PPARα (EC50=30 μM). Fenofibrate at a low dose inhibits CYP2C8 activity without PPARα activation[2]. |
| In Vivo |
Daily intake of Fenofibrate at this low dose (10 μg/g/day) inhibits retinal and choroidal neovascularization induced by CYP2C8 overexpression by 29% (P=0.021) and 36% (P=1.2×10?9) respectively[2]. |
| 动物实验 |
Mice[2] The mouse oxygen-induced retinopathy (OIR) model is used. Briefly to induce retinal neovascularization， mouse pups and their nursing mother are exposed to 75±3% oxygen from P7 to P12. For the higher dose Fenofibrate (F6020) treatment (100 mg/kg/day). Fenofibrate is dissolved in corn oil to make 100mg/mL solution and pure corn oil is used as vehicle control. For the lower dose treatment (10 mg/kg/day)， Fenofibrate is dissolved in 10% DMSO， D2650 to make a 10 mg/mL solution and 10% DMSO is used as vehicle control. After return to room air， mice are orally gavaged with Fenofibrate (100 or 10 mg/kg) or vehicle control daily from P12 to P16. At P17， eyes are enucleated immediately after euthanasia and fixed in 4% paraformaldehyde in PBS for 1 h at room temperature. Retinas are then dissected and stained overnight with Alexa Fluor 594 conjugated isolectin GS-IB4 (10 μg/mL) at room temperature. After washing with PBS， retinas are mounted onto microscope slides with photoreceptor side down and embedded in SlowFade antifade mounting medium. Retinal images are taken using a fluorescence microscope with image software. Retinal neovascularization is analyzed. |
| 激酶实验 |
The half-maximal inhibitory concentrations (IC50s) of Fenofibrate， statins (atorvastatin， lovastatin， pravastatin， simvastatin and simvastatin acid， the active form of simvastatin) and glipizide for recombinant human CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， and CYP3A4 are determined using fluorometric CYP450 inhibition assays. Briefly， the drugs are dissolved in methanol or acetonitrile. In 96 well assay plates， the drugs are diluted to a series of concentrations in a solution containing cofactors including NADP+ (final concentration 1.3 mM)， MgCl2 (final concentration 3.3 m M)， glucose-6-phosphate (G6P， final concentration 3.3 mM) and glucose 6-phosphate dehydrogenase (final concentration 0.4 U/mL). The mixture is pre-incubated at 37°C for 10 min. The enzymes and fluorogenic substrates are diluted to desired concentrations in sodium phosphate reaction buffer (pH 7.4， final concentration 200 mM) and mixed. Reactions are initiated with addition of the enzyme and substrate mixture to the cofactor and drug mixture. The final reaction volume of all assays is 200 μL. After incubating at 37°C for a pre-specified period of time (15 to 45 min)， the reactions are stopped with addition of 75 μL quenching solution (0.5 M Tris base or 2N NaOH). Fluorescence is determined using a BioTek Synergy 2 fluorescence reader. Each of the drugs is tested at eight concentrations in duplicate. To estimate IC50s， percent of inhibition is calculated using net fluorescence that is corrected for the background. The values of percent of inhibition are then fitted to a three or four parameter log-logistic model[1]. |
| 数据来源文献 |
[1]. Schelleman H， et al. Pharmacoepidemiologic and in vitro evaluation of potential drug-drug interactions of sulfonylureas with fibrates and statins. Br J Clin Pharmacol. 2014 Sep;78(3):639-48.
[2]. Gong Y， et al. Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis. EBioMedicine. 2016 Sep 30. pii: S2352-3964(16)30448-0. |
| 规格 |
0.1ml 0.3ml 0.5ml 1ml 1.5ml |
| 单位 |
瓶 |
中文
英语
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