Fenofibrate - Cytochrome P450 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFenofibrateCat. No.: HY-17356CAS No.: 49562-28-9分式: CHClO分量: 360.83作靶点: Cytochrome P450; PPAR; Autophagy作通路: Metabolic Enzyme/Protease; Cell Cycle/DNA Damage;Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20

2、C 1 month溶解性数据体外实验 DMSO : 47 mg/mL (130.26 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.7714 mL 13.8569 mL 27.7139 mL5 mM 0.5543 mL 2.7714 mL 5.5428 mL10 mM 0.2771 mL 1.3857 mL 2.7714 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选

3、择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： corn oilSolubility: 33.33 mg/mL (92.37 mM); Clear solution; Need ultrasonicBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 Fenofibrate是PPAR 激动剂，EC50 为30

4、M。IC50 & Target CYP2C19 CYP2B6 CYP2C9 CYP2C80.2 M (IC50) 0.7 M (IC50) 9.7 M (IC50) 4.8 M (IC50)CYP3A4 PPAR142.1 M (IC50) 30 M (IC50)体外研究 Fenofibrate is a relatively potent inhibitor of CYP2B6 (IC50=0.70.2 M) and CYP2C19 (IC50=0.20.1 M).Fenofibrate is also a moderate inhibitor of CYP2C8 (IC50=4.81.7

5、M) and CYP2C9 (IC50=9.7 M) 1.Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPAR.Fenofibrate is a well-known PPAR agonist, but an in vitro assessment of 209 frequently prescribed drugs andrelated xenobiotics suggests that Fenofibrate is also a pote

6、nt inhibitor of cytochrome P450 epoxygenase(CYP)2C. The affinity of Fenofibrate to CYP2C is 10 times higher (EC50=2.390.4 M) than to PPAR (EC50=30 M). Fenofibrate at a low dose inhibits CYP2C8 activity without PPAR activation 2.体内研究 Daily intake of Fenofibrate at this low dose (10 g/g/day) inhibits

7、retinal and choroidal neovascularizationinduced by CYP2C8 overexpression by 29% (P=0.021) and 36% (P=1.2109) respectively 2.PROTOCOLKinase Assay 1 The half-maximal inhibitory concentrations (IC50s) of Fenofibrate, statins (atorvastatin, lovastatin,pravastatin, simvastatin and simvastatin acid, the a

8、ctive form of simvastatin) and glipizide for recombinanthuman CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 are determined usingfluorometric CYP450 inhibition assays. Briefly, the drugs are dissolved in methanol or acetonitrile. In 96 wellassay plates, the drugs are diluted to a series

9、 of concentrations in a solution containing cofactors includingNADP+ (final concentration 1.3 mM), MgCl2 (final concentration 3.3 m M), glucose-6-phosphate (G6P, finalconcentration 3.3 mM) and glucose 6-phosphate dehydrogenase (final concentration 0.4 U/mL). The mixtureis pre-incubated at 37C for 10

10、 min. The enzymes and fluorogenic substrates are diluted to desiredconcentrations 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

11、 all assays is 200 L. After incubating at 37C for a pre-specified period of time(15 to 45 min), the reactions are stopped with addition of 75 L quenching solution (0.5 M Tris base or 2NNaOH). Fluorescence is determined using a BioTek Synergy 2 fluorescence reader. Each of the drugs istested at eight

12、 concentrations in duplicate. To estimate IC50s, percent of inhibition is calculated using netfluorescence that is corrected for the background. The values of percent of inhibition are then fitted to a threeor four parameter log-logistic model 1.MCE has not independently confirmed the accuracy of th

13、ese methods. They are for reference only.Animal Mice 2Administration 2 The mouse oxygen-induced retinopathy (OIR) model is used. Briefly to induce retinal neovascularization,mouse pups and their nursing mother are exposed to 753% oxygen from P7 to P12. For the higher doseFenofibrate (F6020) treatmen

14、t (100 mg/kg/day). Fenofibrate is dissolved in corn oil to make 100mg/mL2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEsolution 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%

15、DMSO is used asvehicle control. After return to room air, mice are orally gavaged with Fenofibrate (100 or 10 mg/kg) or vehiclecontrol 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

16、dissected and stained overnight withAlexa Fluor 594 conjugated isolectin GS-IB4 (10 g/mL) at room temperature. After washing with PBS,retinas are mounted onto microscope slides with photoreceptor side down and embedded in SlowFadeantifade mounting medium. Retinal images are taken using a fluorescenc

17、e microscope with image software.Retinal neovascularization is analyzed.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Hepatology. 2018 Jul;68(1):289-303.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Schelleman H, et al. Pharmacoepidemiologic and in vitro evaluation of potential drug-drug interactions of sulfonylureas with fibrates andstatins. 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 Ocu