切换导航

VX-702

现货
Catalog No.
A8687
P38α MAPK高度选择性、ATP竞争性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 500.00
现货
25mg
¥ 700.00
现货
50mg
¥ 1,280.00
现货
100mg
¥ 1,900.00
现货
200mg
¥ 2,900.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

VX-702 is a selective inhibitor of p38α MAPK with IC50 value ranges from 4 nM to 20 nM [1].

P38 mitogen-activated protein kinases (p38 MAPK), also named as MAPK14, are a class of mitogen-activated protein kinases and play an important role in a signaling cascade controlling cellular responses to cytokines and stress [1-3].

VX-702 is a potent p38α MAPK inhibitor and is designed as for greater affinity and greater selectivity compared with the first reported p38α MAPK inhibitors. When tested with PLTs (platelets), VX-702 caused better maintenance of PLT mitochondrial, functional, structural and metabolic parameters during 7 days storage and restored PLTs properties following an extended interruption of agitation to levels of continuously agitated PLTs [2, 4].

In the isolated perfused rat kidney (IPRK) model, administration of VX-702 at a range of doses between 100 and 600 ng/mL showed linear excretion and the clearance data were consistent with net reabsorption by the kidney. Further, VX-702 was showed not a substrate for renal organic anion and organic cation transport systems [3].

References:
[1].  Kuliopulos, A., R. Mohanlal, and L. Covic, Effect of selective inhibition of the p38 MAP kinase pathway on platelet aggregation. Thromb Haemost, 2004. 92(6): p. 1387-93.
[2].  Skripchenko, A., et al., An inhibition of p38 mitogen activated protein kinase delays the platelet storage lesion. PLoS One, 2013. 8(8): p. e70732.
[3].  Tamhane, M., et al., Comparative renal excretion of VX-702, a novel p38 MAPK inhibitor, and methotrexate in the perfused rat kidney model. Drug Dev Ind Pharm, 2010. 36(3): p. 315-22.
[4].  Wagner, S.J., et al., Amelioration of lesions associated with 24-hour suboptimal platelet storage at 16 degrees C by a p38MAPK inhibitor, VX-702. Vox Sang, 2015. 108(3): p. 226-32.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt404.33
Cas No.479543-46-9; 745833-23-2
FormulaC19H12F4N4O2
Solubility≥20.2mg/mL in DMSO
Chemical Name6-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)pyridine-3-carboxamide
SDFDownload SDF
Canonical SMILESC1=CC(=C(C(=C1)F)N(C2=NC(=C(C=C2)C(=O)N)C3=C(C=C(C=C3)F)F)C(=O)N)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议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。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

血小板

溶解方法

该化合物在DMSO中的溶解度大于20.2 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

IC50: 4-20 nM

应用

在用LPS引发的离体血液测定中,VX-702以剂量依赖方式抑制IL-6、IL-1β和TNFα的产生,IC50分别59、122和99 ng/ml。从健康个体制备凝胶过滤的血小板中,用1 μM VX-702预孵育完全或部分抑制血小板活化,IC50为4-20 nM。在存在或不存在血小板抑制剂如阿司匹林、肝素或apyrase的情况下,VX-702对由p38MAPK激动剂如凝血酶、SFLLRN、AYPGKF和胶原诱导的血小板聚集没有影响。VX-702不直接引起血小板聚集或诱导Ca2+动员以及影响剪切应激引起的基底聚集。VX-702对血小板功能没有显著影响,估计也不会引起治疗患者血液学副作用的风险升高。

动物实验 [1]:

动物模型

胶原诱导的关节炎小鼠模型

给药剂量

口服,0.1 mg/kg,5 mg/kg,每天两次

应用

在胶原诱导的关节炎小鼠模型中,每天两次0.1 mg/kg VX-702效果与0.1 mg/kg的methotrexate效果相当,methotrexate是常用的抗风湿药物。在相同模型中,通过腕关节侵蚀的抑制百分比和炎症评分测量发现,每日两次5 mg/kg VX-702效果相当于每天一次prednisolone(10 mg/kg)。将缺血再灌注损伤后心肌损伤的雄性Sprague Dawley大鼠随机分为接受对照或VX-702(5或50 mg/kg),结果表明,与非局部缺血组织相比,缺血组织中的荧光MK2明显增加。该作用在VX-702组中以剂量依赖性方式降低。VX-702选择性抑制缺血后p38 MAPK的活化,对ERK和JNK无影响。50-mg/kg组MI/AAR比值明显低于其他两组。口服VX-702可减少缺血再灌注损伤后的心肌损伤。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Ding C. Drug evaluation: VX-702, a MAP kinase inhibitor for rheumatoid arthritis and acute coronary syndrome[J]. Current opinion in investigational drugs, 2006, 7(11): 1020-1025.

生物活性

Description VX-702是P38α MAPK高度选择性抑制剂。
靶点 p38α          
IC50 4 nM-20 nM          

质量控制