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MK 886 (Synonyms: L 663536)
目录号: PC11580 纯度: ≥98%
CAS No. :118414-82-7
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中文名称
MK 886
中文别名
3-[1-(4-氯苄基)-3-叔丁基硫代-5-异丙基吲哚-2-基]-2,2-二甲基丙酸;1-[(4-氯苯基)甲基]-3-叔丁基硫基-alpha,alpha-二甲基-5-异丙基-1H-吲哚-2-丙酸;MK-886
英文名称
MK 886
英文别名
3-(3-(tert-Butylthio)-1-(4-chlorobenzyl)-5-isopropyl-1H-indol-2-yl)-2,2-dimethylpropanoic acid;1H-Indole-2-propanoicacid, 1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-a,a-dimethyl...;1H-Indole-2-propanoicacid, 1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-a,a-dimethyl-5-(1-methylethyl)-;3-[3-tert-butylsulfanyl-1-[(4-chlorophenyl)methyl]-5-propan-2-ylindol-2-yl]-2,2-dimethylpropanoic acid;MK 886;MK-886;BC-105;L 663536;L-663536;Litec;MK866;Pizotifen;Pizotifene;Pizotifeno;Pizotifenum;PIZOTYLINE;Polomigran;Sandomigran;Sandomygran;SIN-1 chloride;CGS-81585;MK-886 (L-663,536);MK-886 (Free Base);3-[1-(4-Chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl]-2,2-dimethylpropanoic acid;3-[3-tert-Butylthio-1-(4-chlorobenzyl)-5-isopropyl-1H-indol-2-yl]-2,2-dimethylpropionic acid;3-[1-(4-Chlorobenzyl)-3-(tert-butylthio)-5-isopropyl-1H-indol-2-yl]-2,2-dimethylpropionic acid;3-[1-(4-Chlorobenzyl)-3-(tert-butylthio)-5-isopropyl-1H-indol-2-yl]-2,2-dimethylpropanoic acid;L-663,536;MK886;QAOAOVKBIIKRNL-UHFFFAOYSA-N;080626SQ8C;1H-Indole-2-propanoic acid, 1-[(4-chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-Alpha,Alpha-dimethyl-5-(1-methylethyl)- [CAS];SMR000466278;3-
Cas No.
118414-82-7
分子式
C27H34ClNO2S
分子量
472.08
包装储存
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
生物活性

MK-886 (L 663536) is a potent, cell-permeable and orally active FLAP (IC50 of 30 nM) and leukotriene biosynthesis (IC50s of 3 nM and 1.1 μM in intact leukocytes and human whole blood, respectively) inhibitor. MK-886 is also a non-competitive PPARα antagonist and can induce apoptosis.

性状

Solid

IC50 & Target[1][2]

IC50: 30 nM (FLAP)
IC50: 3 nM (Leukotriene biosynthesis in intact leukocytes) and 1.1 μM (Leukotriene biosynthesis in human whole blood)
PPARα

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.
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.
Although Jurkat cells express all PPAR isoforms, various PPARα and PPARγ agonists are unable to prevent MK-886-induced apoptosis.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis

Cell Line: Primary keratinocytes
Concentration: 0.5 μM, 1 μM or 2 μM
Incubation Time: 15?hours
Result: Decreased in keratin-1 expression.
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.
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.

Medlife has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Male Sprague-Dawley rats (300-400 g) with antigen-induced dyspnea
Dosage: 5 mg/kg
Administration: Oral administration
Result: Inhibited the antigen-induced dyspnea.
运输条件

Room temperature or refrigerated transportation.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
参考文献
溶解度数据
体外研究: 

DMSO : 75 mg/mL (158.87 mM; Need ultrasonic)

配制储备溶液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
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
*

产品不同,其溶解度不同。建议根据产品选择合适的溶剂配制储备溶液;配成溶液后,建议分装保存,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,建议在 6 个月内使用,-20°C 储存时,建议在 1 个月内使用。

体内研究:

建议根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都建议先按照 体外研究 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.

    建议依照次序添加每种溶剂: 0.5% CMC-Na/saline water

    Solubility: 10 mg/mL (21.18 mM); Suspended solution; Need ultrasonic

  • 2.

    建议依照次序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in 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 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
  • 3.

    建议依照次序添加每种溶剂: 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。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH?O 中,得到澄清透明的生理盐水溶液
  • 4.

    建议依照次序添加每种溶剂: 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。

*
搜索质检报告(COA)

1:一般建议:溶解度为Medlife测试数据,可能与文献描述存在差异。这是由于生产工艺和批次不同产生的正常现象。为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同批次产品溶解度各有差异,仅做参考,具体以实验方案为准。

2:储存条件:粉末-20°C一般情况可以保存3年,溶于溶剂-80°C一般情况可以保存1年。不同产品及不同批次产品可能存在差异,请细致阅读产品信息,并辅助参考相关文献描述。

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