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.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

360.83

C₂₀H₂₁ClO₄

49562-28-9

非诺贝特

Room temperature in continental US; may vary elsewhere.

DMSO : 250 mg/mL (692.85 mM; Need ultrasonic)

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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： corn oil

  Solubility: 33.33 mg/mL (92.37 mM); Clear solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (6.93 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.93 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: 2.5 mg/mL (6.93 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (6.93 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 4.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (6.93 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.93 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [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.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.