VX-11e
(Synonyms: VX 11e, VX11e) 目录号 : GC13115
A selective ERK inhibitor
Cas No.:896720-20-0
Sample solution is provided at 25 µL, 10mM.
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VX-11e is a potent, selective, and orally bioavailable inhibitor of ERK with Ki < 2 nM.
VX-11e is active in the HT29 cell proliferation assay (IC50=48 nM)[1].
VX-11e is orally bioavailable in both rat and mice[1]. VX-11e (50 mg/kg, p.o.) results in robust inhibition of pRSK, and inhibits tumor growth in NSG mice bearing human melanoma RPDX tumors. VX-11e with BKM120 significantly improves tumor growth inhibition[2].
References:
[1]. Aronov, Alex M., 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, 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.
| Kinase experiment [1]: | |
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ERK inhibition assay |
Compounds were assayed for the inhibition of ERK2 by a spectophotometric coupled-enzyme assay. In this assay, a fixed concentration of activated ERK2 (10 nM) was incubated with various concentrations of the compounds in DMSO (2.5%) for 10 mins at 30 ℃ in 0.1 M HEPES buffer, pH = 7.5, containing 10 mM MgCl2, 2.5 mM phosphoenolpyruvate, 200 μM NADH, 150 μg/mL pyruvate kinase, 50 μg/mL lactate dehydrogenase and 200 μM erktide peptide. The reaction was initiated by the addition of 65 μM ATP. The rate of decrease of absorbance at 340 nM was monitored. The IC50 was evaluated from the data as a function of inhibitor concentration. |
| Cell experiment [1]: | |
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Cell lines |
HT29 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reaction Conditions |
≤ 10 μM; 48 hrs |
|
Applications |
In HT29 cells, VX-11e potently inhibited cell proliferation with an IC50 value of 48 nM. |
| Animal experiment [2]: | |
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Animal models |
NSG mice bearing human melanoma RPDX tumors |
|
Dosage form |
50 mg/kg; p.o.; b.i.d. |
|
Applications |
In NSG mice bearing human melanoma RPDX tumors, VX-11e (50 mg/kg, p.o.) potently inhibited pRSK and tumor growth. VX-11e, combined with BKM120, resulted in significantly improved tumor growth inhibition. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 896720-20-0 | SDF | |
| 别名 | VX 11e, VX11e | ||
| 化学名 | 4-[2-(2-chloro-4-fluoroanilino)-5-methylpyrimidin-4-yl]-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide | ||
| Canonical SMILES | CC1=CN=C(N=C1C2=CNC(=C2)C(=O)NC(CO)C3=CC(=CC=C3)Cl)NC4=C(C=C(C=C4)F)Cl | ||
| 分子式 | C24H20Cl2FN5O2 | 分子量 | 500.35 |
| 溶解度 | ≥ 25 mg/mL in DMSO, ≥ 12.65 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9986 mL | 9.993 mL | 19.986 mL |
| 5 mM | 0.3997 mL | 1.9986 mL | 3.9972 mL |
| 10 mM | 0.1999 mL | 0.9993 mL | 1.9986 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet