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VX-11e

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Chemical Structure| 896720-20-0 同义名 : TCS ERK 11e;Vertex-11e;ERK-11e;TCS Extracellular Signal-Related Kinase 11e;VTX-11e
CAS号 : 896720-20-0
货号 : A260385
分子式 : C24H20Cl2FN5O2
纯度 : 99%+
分子量 : 500.352
MDL号 : MFCD18433366
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(209.85 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • ERK2

    ERK2, Ki:<2 nM
描述 Extracellular signal-regulated kinases (ERKs) are protein kinase intracellular signaling molecules that participate in Ras-Raf-MEK-ERK signal transduction cascade, which is related with the regulation of various processes including cell adhesion, cell cycle progression, cell migration, cell survival, differentiation, metabolism, proliferation, and transcription[3]. VX-11e is an ERK inhibitor with IC50 value of 17 nM and 15 nM on ERK1 and ERK2, respectively[4]. While VX-11e was tested for cytotoxic activity on A549 and DM122, they EC50 value is 770 nM and 370 nM after four days of incubation. The ERK1/2 phosphorylation level analyzed by western blot assay showed enhancement at both 0.5 μM and 2μM of vx-11e[4]. In human melanoma RPDX tumor expanded NSG mice, the vx-11e was given 50 mg/kg BID for 2 weeks. VX-11 could inhibit the tumor growth significantly compared to control, and the PI3K expression level measured by western blot assay was inhibited in the tumor tissue[5].
作用机制 The vx-11e can bind with the inactive, unphosphorylated and active, phosphorylated ERK2. The equilibrium between the T and R-state conformers formed by the inhibitor with the inactive and active enzyme is strongly shifts to favor the R form. Thus, the allosteric properties of ERK2 endow the active form of the kinase with a novel capability of being inhibited through mechanisms involving conformational selection[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HT-29 cells Proliferation assay Antiproliferative activity against human HT-29 cells, IC50=0.048 μM 19827834
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.00mL

0.40mL

0.20mL

9.99mL

2.00mL

1.00mL

19.99mL

4.00mL

2.00mL
参考文献

[1]Krepler C, Xiao M, 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.

[2]Aronov AM, Tang Q, et al. Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control. J Med Chem. 2009 Oct 22;52(20):6362-8.

[3]Roskoski R Jr. ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res. 2012 Aug;66(2):105-43.

[4]Shin M, Franks CE, Hsu KL. Isoform-selective activity-based profiling of ERK signaling. Chem Sci. 2018 Feb 6;9(9):2419-2431.

[5]Krepler C, Xiao M, Sproesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos PI, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. 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.

[6]Rudolph J, Xiao Y, Pardi A, Ahn NG. Slow inhibition and conformation selective properties of extracellular signal-regulated kinase 1 and 2 inhibitors. Biochemistry. 2015 Jan 13;54(1):22-31.