| 名称 | Fenofibrate |
| 描述 | Fenofibrate (Lipanthyl) is a PPARα agonist (EC50=30 μM) and is selective. Fenofibrate also inhibits cytochrome P450 isoforms, such as CYP2C19, CYP2B6, CYP2C9, CYP2C8, and CYP3A4. Fenofibrate exhibits antihyperlipidemic activity. |
| 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]. |
| 体外活性 | 方法：人胶质母细胞瘤细胞系 LN-229 用 Fenofibrate (50 µM) 处理 24 h，通过细胞外通量分析仪测定对 OCR 和 ECAR 的影响。
结果：Fenofibrate 的持续存在导致 OCR 严重受损，并且对任何代谢毒素都没有反应。相比之下，Fenofibrate 预处理细胞的初始 ECAR 值几乎比对照组高 3 倍。[1]
方法：Hep3B、HepG2、HSC-3 和 CH27 细胞用 Fenofibrate (12.5-2000 µM) 处理 24-48 h，通过 Trypan blue exclusion assay 检测细胞活力。
结果：用 Fenofibrate 处理 Hep3B 细胞 24 或 48 h 可产生显著的细胞毒性作用，这些细胞毒性作用是时间依赖性的，但不是剂量依赖性的。Fenofibrate 对 HepG2 细胞没有明显的细胞毒性作用。Fenofibrate 对 HSC-3 和 CH27 细胞具有细胞毒性作用。然而，Hep3B 细胞对 Fenofibrate 杀死细胞的敏感性明显高于 CH27 和 HSC-3 细胞。[2] |
| 体内活性 | 方法：为研究对饮食诱导肥胖 (DIO) 小鼠骨骼肌和内脏白色脂肪组织代谢的影响，将 Fenofibrate (50 mg/kg) 灌胃给药给高脂肪饮食的 C57BL/6J 小鼠，每天一次，持续两周。
结果：在 DIO 小鼠中，Fenofibrate 通过增加能量消耗来防止 HFD 喂养引起的体重增加；改善全身葡萄糖稳态，在骨骼肌中，增加胰岛素依赖性葡萄糖摄取、miR-1a 水平、减少肌肉内脂质积累和磷酸化 AMPKα2 水平。Fenofibrate 对体重、葡萄糖稳态和肌肉代谢的有益作用可能与其在脂肪组织中的作用有关。[3] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : 36.1 mg/mL (100.05 mM), Sonication is recommended.
DMSO : 100 mg/mL (277.14 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5.5 mg/mL (15.24 mM), Solution.
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| 关键字 | PPARα | PPAR | Peroxisome proliferator-activated receptors | Inhibitor | inhibit | Fenofibrate | Cytochrome P450 | CYPs | CYP2C19 | CYP2C | CYP2B6 | Autophagy |
| 相关产品 | Guanidine hydrochloride | Naringin | Daidzein | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Hemin | Hydroxychloroquine | Sildenafil citrate | Stavudine | Tamoxifen | Paeonol |
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