MK-886 (L 663536) 是一种有效的，细胞可渗透的且具有口服活性的 FLAP (IC50为 30 nM) 和白三烯生物合成 (完整白细胞和人全血中的IC50分别为 3 nM 和 1.1μM) 的抑制剂。MK-886 也是一种非竞争性PPARα拮抗剂，可以诱导细胞凋亡。
| 生物活性 | MK-886 (L 663536) is a potent, cell-permeable and orally activeFLAP(IC50of 30 nM) andleukotriene biosynthesis(IC50s of 3 nM and 1.1 μM in intact leukocytes and human whole blood, respectively) inhibitor. MK-886 is also a non-competitivePPARαantagonist and can induceapoptosis[1][2][3]. |
| IC50& Target | IC50: 30 nM (FLAP)[3]
IC50: 3 nM (Leukotriene biosynthesis in intact leukocytes) and 1.1 μM (Leukotriene biosynthesis in human whole blood)[2]
PPARα[1] |
体外研究
(In Vitro) | MK-886 (0.5-2 μM; 15 hours; primary keratinocytes) treatment reduces keratin-1 expression in a culture of mouse primary keratinocytes[1].
Using a transient transfection system in monkey kidney fibroblast CV-1 cells, mouse keratinocyte 308 cells and human lung adenocarcinoma A549 cells, 10 μM MK-886 is able to inhibit Wy-14643 activation of PPARα by ~80%. MK-886 also decreases PPARα activation by fatty acids in the stable transfection system[1].
Although Jurkat cells express all PPAR isoforms, various PPARα and PPARγ agonists are unable to prevent MK-886-induced apoptosis[1].
Western Blot Analysis[1] | Cell Line: | Primary keratinocytes | | Concentration: | 0.5 μM, 1 μM or 2 μM | | Incubation Time: | 15 hours | | Result: | Decreased in keratin-1 expression. |
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体内研究
(In Vivo) | MK-886 (L 663536; 5 mg/kg; oral administration; male Sprague-Dawley rats) treatment potently inhibits the antigen-induced dyspnea in inbred rats pretreated with methysergide[2].
MK-886 (L 663536) inhibits leukotriene biosynthesis in vivo in a rat pleurisy model (ED50, 0.2 mg/kg p.o.), an inflamed rat paw model (ED50, 0.8 mg/kg), a model of leukotriene excretion in rat bile following antigen provocation[2].
| Animal Model: | Male Sprague-Dawley rats (300-400 g) with antigen-induced dyspnea[1] | | Dosage: | 5 mg/kg | | Administration: | Oral administration | | Result: | Inhibited the antigen-induced dyspnea. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 75 mg/mL(158.87 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.1183 mL | 10.5914 mL | 21.1828 mL | | 5 mM | 0.4237 mL | 2.1183 mL | 4.2366 mL | | 10 mM | 0.2118 mL | 1.0591 mL | 2.1183 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；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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 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： 0.5%CMC-Na/saline water Solubility: 10 mg/mL (21.18 mM); Suspended solution; Need ultrasonic 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (5.30 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (5.30 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 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.08 mg/mL (4.41 mM); Clear solution; Need ultrasonic
此方案可获得 2.08 mg/mL (4.41 mM) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 4. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.41 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.41 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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