FLAP/5-lipoxygenase-activating protein (IC50 = 1.6 nM)[1]

Quiflapon 可在人类、松鼠猴和大鼠的全血中获得（IC50 值分别为 510、69 和 9 nM），以及完整的人类和诱导大鼠多形核白细胞 (PMNL)（IC50 值分别为 3.1 和 6.1 nM，分别）。大鼠 5-脂氧合酶不受 quilapon 影响。 Quiflapon 具有光亲和标记，可使用两种不同的光亲和配体抑制 5-脂氧合酶激活蛋白 (FLAP)。它对 FLAP 表现出高亲和力，在 FLAP 结合测定中 IC50 值为 1.6 nM。在人 PMNL 中，可以阻断 5-脂氧合酶从细胞质到膜的易位，以防止 5-脂氧合酶激活 [1]。

Quiflapon 已被证明在三种不同的情况下是体内 LT 生物合成的强抑制剂：对经过治疗的大鼠和松鼠猴抽取的血液进行离体激发、大鼠胸膜炎模型以及抑制尿液中 LTE4 的排泄。对过敏羊进行过敏原检测。 Quiflapon被发现对蛔虫攻击的绵羊、蛔虫攻击的松鼠猴和用methierg预处理的近交大鼠中的抗原诱导的支气管收缩（早期和晚期反应）具有抑制作用[1]。在第 1-4、5-9 或 10-14 天，幼犬每天接受 10、20 或 40 mg/kg 的媒介物或 Quiflapon 皮下注射。第 14 天，对肺部进行充气、固定和染色，以进行形态测量和组织学研究。未治疗的高氧组和 Quiflapon 治疗的高氧组均表现出明显的异常肺泡化迹象，但没有任何炎症 [2]。

在每个实验中，等量的细胞被镀在六孔板中;24 h后取出培养液，加入含有MK-591 (1 μM, 10 μM或25 μM)或载体的新鲜培养液。孵育24小时后，收集上清液用于测定Aβ和LDH，并在裂解缓冲液中收集细胞颗粒用于免疫印迹分析，如前几段所述。 在转染研究中，使用Lipofectamine 2000 (Invitrogen)将1 μg myc标记的mΔE-Notch-1互补DNA转染N2A-APPswe细胞过夜。除去培养基，加入含有MK-591、L685,458或车辆的新鲜培养基。孵育24小时后，收集细胞裂解液，用western blot分析NICD表达水平。[3]

MK-0591 was a potent inhibitor of LT biosynthesis in vivo, first, following ex vivo challenge of blood obtained from treated rats and squirrel monkeys, second, in a rat pleurisy model, and, third, as monitored by inhibition of the urinary excretion of LTE4 in antigen-challenged allergic sheep. Inhibition of antigen-induced bronchoconstriction by MK-0591 was observed in inbred rats pretreated with methysergide, Ascaris-challenged squirrel monkeys, and Ascaris-challenged sheep (early and late phase response).[1]

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Newborn mice were exposed to either room air or hyperoxia for 14 days. Pups were treated with either vehicle or MK-0591 10, 20, or 40 mg/kg subcutaneously daily for days 1-4, 5-9, or 10-14. On day 14, the lungs were inflated, fixed, and stained for histopathological and morphometric analyses. Hyperoxia groups treated with MK-0591 20 or 40 mg/kg during days P1-P4 or P10-P14 showed alveolarization that resembled that of room air controls while untreated hyperoxia groups showed definite evidence of aberrant alveolarization but no inflammation. In a hyperoxia-exposed newborn mice model, a FLAP inhibitor given during critical window periods may prevent aberration of alveolarization in a dose- and time-dependent manner.[2]

[1]. Pharmacology of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid), a potent, orally active leukotriene biosynthesis inhibitor. Can J Physiol Pharmacol. 1992 Jun;70(6):799-8.

[2]. 5-Lipoxygenase-activating protein (FLAP) inhibitor MK-0591 prevents aberrant alveolarization in newborn mice exposed to 85% oxygen in a dose- and time-dependent manner. Lung. 2011 Feb;189(1):43-50.

MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid, previously L-686,708) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human and elicited rat polymorphonuclear leukocytes (PMNLs) (IC50 values 3.1 and 6.1 nM, respectively) and in human, squirrel monkey, and rat whole blood (IC50 values 510, 69, and 9 nM, respectively). MK-0591 had no effect on rat 5-lipoxygenase. MK-0591 has a high affinity for 5-lipoxygenase activating protein (FLAP) as evidenced by an IC50 value of 1.6 nM in a FLAP binding assay and inhibition of the photoaffinity labelling of FLAP by two different photoaffinity ligands. Inhibition of activation of 5-lipoxygenase was shown through inhibition of the translocation of the enzyme from the cytosol to the membrane in human PMNLs. MK-0591 was a potent inhibitor of LT biosynthesis in vivo, first, following ex vivo challenge of blood obtained from treated rats and squirrel monkeys, second, in a rat pleurisy model, and, third, as monitored by inhibition of the urinary excretion of LTE4 in antigen-challenged allergic sheep. Inhibition of antigen-induced bronchoconstriction by MK-0591 was observed in inbred rats pretreated with methysergide, Ascaris-challenged squirrel monkeys, and Ascaris-challenged sheep (early and late phase response). These results indicate that MK-0591 is a potent inhibitor of LT biosynthesis both in vitro and in vivo indicating that the compound will be suitable for assessing the role of leukotrienes in pathological situations.[1]

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Bronchopulmonary dysplasia is characterized by prolonged oxygen dependency due to compromised gas-exchange capability. This is attributable mainly to inadequate and aberrant alveolarization resulting from insults like hyperoxia. Leukotrienes are associated with hyperoxia-induced inhibition of alveolarization. We hypothesized that a 5-lipoxygenase-activating protein (FLAP) inhibitor given while newborn mice were exposed to 85% oxygen would prevent aberrant alveolarization in a dose- and time-dependent manner. Newborn mice were exposed to either room air or hyperoxia for 14 days. Pups were treated with either vehicle or MK-0591 10, 20, or 40 mg/kg subcutaneously daily for days 1-4, 5-9, or 10-14. On day 14, the lungs were inflated, fixed, and stained for histopathological and morphometric analyses. Hyperoxia groups treated with MK-0591 20 or 40 mg/kg during days P1-P4 or P10-P14 showed alveolarization that resembled that of room air controls while untreated hyperoxia groups showed definite evidence of aberrant alveolarization but no inflammation. In a hyperoxia-exposed newborn mice model, a FLAP inhibitor given during critical window periods may prevent aberration of alveolarization in a dose- and time-dependent manner.[2]

C34H35CLN2O3S

587.17100

586.205

C, 69.55; H, 6.01; Cl, 6.04; N, 4.77; O, 8.17; S, 5.46

136668-42-3

Quiflapon sodium;147030-01-1

60923

White to off-white solid powder

1.2±0.1 g/cm3

751.3±60.0 °C at 760 mmHg

408.2±32.9 °C

0.0±2.6 mmHg at 25°C

1.617

8.31

89.65

1

5

10

41

873

0

O=C(O)C(C)(C)CC1=C(SC(C)(C)C)C2=C(C=CC(OCC3=NC4=CC=CC=C4C=C3)=C2)N1CC5=CC=C(Cl)C=C5

NZOONKHCNQFYCI-UHFFFAOYSA-N

InChI=1S/C34H35ClN2O3S/c1-33(2,3)41-31-27-18-26(40-21-25-15-12-23-8-6-7-9-28(23)36-25)16-17-29(27)37(20-22-10-13-24(35)14-11-22)30(31)19-34(4,5)32(38)39/h6-18H,19-21H2,1-5H3,(H,38,39)

3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid

Quiflapon free acid; MK 591; MK-591; MK591; L 686708; L-686708; L686708; L-686,708; L 686,708; Quiflapon; 136668-42-3; MK-0591; Quiflapon [INN]; Quiflapon free acid; 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoic acid; MK 591; CHEMBL16596; L686,708;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~85.15 mM)

配方 1 中的溶解度: 2.5 mg/mL (4.26 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液； 超声和加热处理
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (4.26 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。