Fenofibrate - Cytochrome P450 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

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

2、C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 47 mg/mL (130.26 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 請根據(jù)您的實驗動物和給藥式選

3、擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： corn oilSolubility: 33.33 mg/mL (92.37 mM); Clear solution; Need ultrasonicBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 Fenofibrate是PPAR 激動劑，EC50 為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)體外研究 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.體內(nèi)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 您邊的抑制劑師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.戶使本產(chǎn)品發(fā)表的科研獻 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