切换导航

VX-11e

现货
Catalog No.
A3931
ERK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
现货
5mg
¥ 900.00
现货
10mg
¥ 1,250.00
现货
50mg
¥ 4,000.00
现货
100mg
¥ 6,000.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

VX-11e is a potent and selective inhibitor of ERK [1].
ERK is extracellular signal-regulated kinases. The Ras/Raf/MEK/ERK signal transduction is an oncogenic pathway related to a variety of human cancers [1].
References:
[1]. Aronov, Alex M, Tang Q, et al. Martinez-Botella, Gabriel et al. Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control. Journal of Medicinal Chemistry, 2009, 52(20): 6362-6368.

文献引用

1. Zheng L, Guo Q, et al. "Transcriptional factor six2 promotes the competitive endogenous RNA network between CYP4Z1 and pseudogene CYP4Z2P responsible for maintaining the stemness of breast cancer cells." J Hematol Oncol. 2019 Mar 4;12(1):23. PMID:30832689
2. Gao L, Guo Q, et al. "MiR-873/PD-L1 axis regulates the stemness of breast cancer cells." EBioMedicine. 2019 Feb 22. pii: S2352-3964(19)30112-4. PMID:30803931
3. Kris Cameron Wood,Peter Saville Winter. "Compositions and Methods for Treating Cancer with JAK2 Activity." US Patent App. 15/027,216, 2016.
4. Zheng, Lufeng, et al. "The 3′ UTR of the pseudogene CYP4Z2P promotes tumor angiogenesis in breast cancer by acting as a ceRNA for CYP4Z1." Breast cancer research and treatment (2015): 1-14. PMID:25701119
5. Winter PS, et al. "RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis." Sci Signal. 2014 Dec 23. PMID:25538080

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt500.35
Cas No.896720-20-0
FormulaC24H20Cl2FN5O2
SynonymsVX 11e, VX11e
Solubility≥25 mg/mL in DMSO, ≥12.65 mg/mL in EtOH with ultrasonic, <2.4 mg/mL in H2O
Chemical Name4-[2-(2-chloro-4-fluoroanilino)-5-methylpyrimidin-4-yl]-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
SDFDownload SDF
Canonical SMILESCC1=CN=C(N=C1C2=CNC(=C2)C(=O)NC(CO)C3=CC(=CC=C3)Cl)NC4=C(C=C(C=C4)F)Cl
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

激酶实验 [1]:

ERK抑制试验

通过分光光度偶联酶试验测定化合物对ERK2的抑制作用。在上述试验中,将固定浓度的活化ERK2 (10 nM) 与不同浓度的化合物(溶于2.5% DMSO)加入到0.1 M HEPES缓冲液(pH = 7.5,含10 mM MgCl2,2.5 mM磷酸烯醇丙酮酸盐,200 μM NADH,150 ?g/mL丙酮酸激酶,50 ?g/mL乳酸脱氢酶和200 ?M erktide多肽)中,将其置于30 ℃孵育10分钟。加入65 ?M ATP开启反应。监测340 nM下的吸光度减少率。根据抑制剂浓度估算IC50值。

细胞实验 [1]:

细胞系

HT29细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

≤ 10 μM;48小时

实验结果

在HT29细胞中,VX-11e有效抑制细胞增殖,其IC50值为48 nM。

动物实验 [2]:

动物模型

携带人黑色素瘤RPDX肿瘤的NSG小鼠

给药剂量

50 mg/kg;口服给药;每日2次

实验结果

在携带人黑色素瘤RPDX肿瘤的NSG小鼠中,VX-11e(50 mg/kg,口服给药)有效抑制pRSK和肿瘤生长。当与BKM120联合使用时,VX-11e的肿瘤生长抑制作用显著提高

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Aronov, Alex M, Tang Q, et al. Martinez-Botella, Gabriel et al. Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control. Journal of Medicinal Chemistry, 2009, 52(20): 6362-6368.

[2]. Krepler C, Xiao M, Sproesser K, et al. Personalized Preclinical Trials in BRAF Inhibitor-Resistant Patient-Derived Xenograft Models Identify Second-Line Combination Therapies. Clin Cancer Res. 2016 Apr 1;22(7):1592-602.

质量控制

化学结构

VX-11e

相关生物数据

VX-11e

相关生物数据

VX-11e

相关生物数据

VX-11e