| 名稱 | 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. |
| 激酶實驗 | 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]. |
| 體外活性 | 方法：人膠質(zhì)母細(xì)胞瘤細(xì)胞系 LN-229 用 Fenofibrate (50 μM) 處理 24 h，通過細(xì)胞外通量分析儀測定對 OCR 和 ECAR 的影響。
結(jié)果：Fenofibrate 的持續(xù)存在導(dǎo)致 OCR 嚴(yán)重受損，并且對任何代謝毒素都沒有反應(yīng)。相比之下，F(xiàn)enofibrate 預(yù)處理細(xì)胞的初始 ECAR 值幾乎比對照組高 3 倍。[1]
方法：Hep3B、HepG2、HSC-3 和 CH27 細(xì)胞用 Fenofibrate (12.5-2000 μM) 處理 24-48 h，通過 Trypan blue exclusion assay 檢測細(xì)胞活力。
結(jié)果：用 Fenofibrate 處理 Hep3B 細(xì)胞 24 或 48 h 可產(chǎn)生顯著的細(xì)胞毒性作用，這些細(xì)胞毒性作用是時間依賴性的，但不是劑量依賴性的。Fenofibrate 對 HepG2 細(xì)胞沒有明顯的細(xì)胞毒性作用。Fenofibrate 對 HSC-3 和 CH27 細(xì)胞具有細(xì)胞毒性作用。然而，Hep3B 細(xì)胞對 Fenofibrate 殺死細(xì)胞的敏感性明顯高于 CH27 和 HSC-3 細(xì)胞。[2] |
| 體內(nèi)活性 | 方法：為研究對飲食誘導(dǎo)肥胖 (DIO) 小鼠骨骼肌和內(nèi)臟白色脂肪組織代謝的影響，將 Fenofibrate (50 mg/kg) 灌胃給藥給高脂肪飲食的 C57BL/6J 小鼠，每天一次，持續(xù)兩周。
結(jié)果：在 DIO 小鼠中，F(xiàn)enofibrate 通過增加能量消耗來防止 HFD 喂養(yǎng)引起的體重增加；改善全身葡萄糖穩(wěn)態(tài)，在骨骼肌中，增加胰島素依賴性葡萄糖攝取、miR-1a 水平、減少肌肉內(nèi)脂質(zhì)積累和磷酸化 AMPKα2 水平。Fenofibrate 對體重、葡萄糖穩(wěn)態(tài)和肌肉代謝的有益作用可能與其在脂肪組織中的作用有關(guān)。[3] |
| 存儲條件 | 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 : 55 mg/mL (152.43 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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| 關(guān)鍵字 | PPARα | PPAR | Peroxisome proliferator-activated receptors | Inhibitor | inhibit | Fenofibrate | Cytochrome P450 | CYPs | CYP2C19 | CYP2C | CYP2B6 | Autophagy |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Daidzein | Gefitinib | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Paeonol | Sodium 4-phenylbutyrate |
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