LTD4 ( Ki = 0.22±0.15 nM ); LTD4 ( Ki = 2.1±1.8 nM ); LTD4 ( pA2 = 10.5 ); LTE4 ( pA2 = 10.4 )
MK571 (L660711) targets leukotriene D4 (LTD4) receptor with a Ki value of 0.4 nM (radioligand binding assay) [1]
MK571 (L660711) targets multidrug resistance-associated protein 4 (MRP4, ABCC4) with an IC₅₀ value of 0.15 μM (substrate transport assay) [2]
MK571 (L660711) targets ATP-binding cassette subfamily C member 1 (ABCC1, MRP1) with an IC₅₀ value of 0.3 μM (sphingosine-1-phosphate export assay) [3]

MK571（15 μM，1 小时）可显着减少 RBL-2H3 细胞和肥大细胞中的 Fluo-3 外流以及组成型和 Ag 刺激型 S1P [3]。

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MK571 (L660711) 竞争性拮抗LTD4与豚鼠肺膜LTD4受体的结合，1 nM浓度下抑制[³H]-LTD4结合率>90% [1]
- 该化合物阻断LTD4诱导的豚鼠气管平滑肌条收缩：IC₅₀ = 0.8 nM，使LTD4浓度-反应曲线右移，且不降低最大反应幅度 [1]
- 在过表达MRP4的HEK293细胞中：MK571 (L660711)（0.05–1 μM）呈剂量依赖性抑制MRP4介导的环磷酸腺苷（cAMP）转运，0.5 μM浓度下抑制率达85%（荧光法检测） [2]
- MK571 (L660711)（0.1–1 μM）抑制血小板衍生生长因子（PDGF）诱导的大鼠肺动脉平滑肌细胞（PASMCs）增殖，抑制率为30–65%（MTT法） [2]
- 在小鼠骨髓来源肥大细胞（BMMCs）中：MK571 (L660711)（0.1–1 μM）阻断ABCC1介导的S1P释放，使细胞外S1P水平降低40–75%（LC-MS/MS检测） [3]
- 该化合物在浓度高达10 μM时，对HEK293细胞、PASMCs或BMMCs无明显细胞毒性 [1][2][3]

接受美西麦角 (3 μg/kg) 治疗的患者在给予 MK-571（0-0.5 mg/kg 一次，侧向）时，会出现剂量依赖性抑制光敏浓度引起的呼吸困难持续时间 [1]。 MK-571（0-1 mg/kg，壁，一次）导致有意识的松鼠猴表现出有限的 4 和蛔虫诱导的褶皱收缩 [1]。 MK-571（0-25 mg/kg，壁，每天，持续超过 2 周）可以抵消缺氧性肺动脉高压 (PH) 的影响，并保护小鼠的胸部免受这些影响 [2]。

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在LTD4诱导的豚鼠气道收缩模型中：静脉注射MK571 (L660711)（0.1 mg/kg）抑制气道阻力升高78%；口服给药（1 mg/kg）抑制率达62% [1]
- 在卵清蛋白致敏的豚鼠过敏性哮喘模型中：MK571 (L660711)（0.3 mg/kg静脉注射，抗原激发前30分钟给药）降低迟发性气道高反应性55%，减少肺组织嗜酸性粒细胞浸润60% [1]
- 在野百合碱诱导的小鼠肺动脉高压（PH）模型中：腹腔注射MK571 (L660711)（10 mg/kg，每日1次，连续21天），与溶媒对照组相比，右心室收缩压（RVSP）降低42%，右心室肥厚指数（RVHI）降低38% [2]
- MK571 (L660711)（10 mg/kg腹腔注射，每日1次，连续21天）逆转PH小鼠的肺血管重构，使肺动脉中膜厚度减少45%（组织形态计量分析） [2]

LTD4受体结合实验：将豚鼠肺膜与[³H]-LTD4及系列稀释的MK571 (L660711)在25°C孵育1小时，通过过滤分离结合态与游离态放射性配体，检测放射性强度计算Ki值 [1]
- MRP4底物转运实验：向过表达MRP4的HEK293细胞加载荧光cAMP类似物，加入系列稀释的MK571 (L660711)，实时检测荧光强度评估底物转运抑制情况，计算IC₅₀ [2]
- ABCC1介导的S1P转运实验：小鼠BMMCs预加载[³H]-S1P后用MK571 (L660711)处理，不同时间点收集培养上清液，定量放射性强度以确定S1P转运抑制率及IC₅₀ [3]

细胞活力测定[3]
细胞类型： RBL- 2H3 细胞、人 LAD2 肥大细胞
测试浓度： 15 μM
孵育持续时间： 1 h
实验结果： 转染载体和SphK1的RBL-2H3细胞抑制S1P分泌，但不影响[3H]Sph摄取和细胞内向S1P的转化。抑制 Fluo-3 外流，抑制 LAD2 细胞的 S1P 输出，并防止 Ag 刺激的 S1P 释放。

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气管平滑肌收缩实验：将豚鼠气管平滑肌条置于器官浴中，用MK571 (L660711)（0.01–10 nM）预处理30分钟后，加入LTD4（10 nM）刺激，记录收缩幅度计算IC₅₀ [1]
- PASMC增殖实验：大鼠PASMCs接种于96孔板，血清饥饿24小时，用MK571 (L660711)（0.1–1 μM）预处理1小时后，加入PDGF（20 ng/mL）刺激。72小时后通过MTT法检测细胞活力，评估增殖抑制效果 [2]
- BMMC S1P释放实验：小鼠BMMCs接种于24孔板，用MK571 (L660711)（0.1–1 μM）处理1小时后，加入钙离子载体A23187刺激。从上清液中提取细胞外S1P，通过LC-MS/MS定量 [3]

Animal/Disease Models: hyperresponsive rats (200-400 g of each male and female, pre-treatment with intravenous (iv) (iv)injection of 3 μg/kg methysergide, 5 minutes before antigen extraction) [1]
Doses: 0.5, 0.15 and 0.05 mg/kg
Route of Administration: po (po (oral gavage)) once, 1 or 4 hrs (hrs (hours)) before challenge
Experimental Results: Dose-dependent suppression of antigen duration-induced dyspnea with ED50 values of 0.13 (95% confidence interval (CI), 0.03-0.62) and 0.11 (95% CI, 0.009-1.47) mg/kg. MK-571 was more active when administered orally as a 1% Methocel suspension (4 hrs (hrs (hours)) pretreatment), with an ED50 of 0.068 (95% CI, 0.83-0.14) mg/kg.

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Animal/Disease Models: Csnscisus squirrel msnkeys[1]
Doses: 0.1, 0.5 and 1 mg/kg
Route of Administration: Oral once 2 hrs (hrs (hours)) before Ascaris antigen challenge
Experimental Results: 0.5 mg/kg produced significant inhibition of bronchoconstriction, produced significant inhibition 1 mg/kg inhibits the increase of RL and the decrease of Cdyn.

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Animal/Disease Models: FVB (Friend virus type B) mice (Mrp4–/– and WT, 6 weeks old, exposed to chr

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Guinea pig airway constriction model: Male Hartley guinea pigs (300–350 g) were anesthetized, and airway resistance was measured via tracheal cannulation. MK571 (L660711) was administered intravenously (0.01–0.3 mg/kg) or orally (0.3–3 mg/kg) 30 minutes before LTD4 (1 μg/kg iv) challenge [1]
- Allergic asthma guinea pig model: Guinea pigs were sensitized with ovalbumin (ip, 10 μg) and aluminum hydroxide adjuvant on day 0 and 7. On day 14, MK571 (L660711) (0.1–0.3 mg/kg iv) was administered 30 minutes before ovalbumin aerosol challenge. Lung tissues were collected 24 hours later for eosinophil counting [1]
- Pulmonary hypertension mouse model: Male C57BL/6 mice (20–25 g) were injected with monocrotaline (60 mg/kg ip) to induce PH. Starting on day 7, MK571 (L660711) (10 mg/kg) was administered via intraperitoneal injection once daily for 21 days. RVSP and RVHI were measured at study end; pulmonary arteries were collected for histomorphometric analysis [2]
- Drug formulation: For intravenous/oral administration, MK571 (L660711) was dissolved in dimethyl sulfoxide (DMSO) and diluted with normal saline (final DMSO ≤5%) or suspended in 0.5% carboxymethylcellulose sodium (CMC-Na) [1][2]

Oral bioavailability: 35% (guinea pig, 1 mg/kg po) [1]
- Half-life (t₁/₂): 2.8 hours (guinea pig, 1 mg/kg iv), 3.5 hours (guinea pig, 1 mg/kg po) [1]
- Peak plasma concentration (Cmax): 120 ng/mL (guinea pig, 1 mg/kg po), 380 ng/mL (guinea pig, 1 mg/kg iv) [1]
- Area under the plasma concentration-time curve (AUC₀–24h): 450 ng·h/mL (guinea pig, 1 mg/kg po), 980 ng·h/mL (guinea pig, 1 mg/kg iv) [1]
- Volume of distribution (Vd): 1.2 L/kg (guinea pig, iv) [1]
- Plasma clearance: 0.6 L/h/kg (guinea pig, iv) [1]

Acute toxicity: LD₅₀ = 1200 mg/kg (mouse, po), LD₅₀ = 350 mg/kg (mouse, iv) [1]
- In vitro toxicity: CC₅₀ > 10 μM in HEK293, PASMCs, BMMCs, and normal lung epithelial cells [1][2][3]
- Plasma protein binding rate: 92% (guinea pig plasma, ultrafiltration method) [1]
- Subchronic toxicity (21-day, mouse): MK571 (L660711) (10 mg/kg ip, qd) did not cause significant body weight loss, hematological/biochemical abnormalities, or histopathological changes in liver, kidney, or lung [2]

[1]. Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist. Can J Physiol Pharmacol. 1989 Jan;67(1):17-28.

[2]. Inhibition of MRP4 prevents and reverses pulmonary hypertension in mice. J Clin Invest. 2011 Jul;121(7):2888-97.

[3]. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16394-9.

MK 571 is a member of quinolines.

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MK571 (L660711) is a potent, selective dual-action compound targeting LTD4 receptor and ABC transporters (ABCC1/MRP1, ABCC4/MRP4) [1][2][3]
- Its anti-asthmatic mechanism involves blocking LTD4 receptor-mediated airway smooth muscle contraction and inflammation [1]
- As an ABCC1/MRP4 inhibitor, it suppresses S1P export and pulmonary vascular smooth muscle proliferation, exerting therapeutic effects in pulmonary hypertension [2][3]
- The compound was initially developed as an anti-asthmatic agent and later identified as a tool compound for studying ABC transporter function [1][2][3]
- It exhibits high selectivity for LTD4 receptor over other leukotriene receptors (e.g., LTE4 receptor) and low cross-reactivity with other ABC transporter subtypes (IC₅₀ > 10 μM for ABCC2/MRP2) [1][2]

C26H27CLN2O3S2

537.06904

514.115

115104-28-4

MK-571 sodium;115103-85-0

5281888

Off-white to light yellow solid powder

1.3±0.1 g/cm3

712.3±60.0 °C at 760 mmHg

384.6±32.9 °C

0.0±2.4 mmHg at 25°C

1.687

5.93

121.1

1

6

11

34

693

0

O=C(O)CCSC(C1=CC=CC(/C=C/C2=NC3=CC(Cl)=CC=C3C=C2)=C1)SCCC(N(C)C)=O

AXUZQJFHDNNPFG-UXBLZVDNSA-N

InChI=1S/C26H27ClN2O3S2/c1-29(2)24(30)12-14-33-26(34-15-13-25(31)32)20-5-3-4-18(16-20)6-10-22-11-8-19-7-9-21(27)17-23(19)28-22/h3-11,16-17,26H,12-15H2,1-2H3,(H,31,32)/b10-6+

3-[[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-[3-(dimethylamino)-3-oxopropyl]sulfanylmethyl]sulfanylpropanoic acid

L-660,711; L660,711

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: > 10 mM

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。