EW-7197
(Synonyms: Vactosertib，TEW-7197) 目录号 : GC13354
A potent inhibitor of ALK5
Cas No.:1352608-82-2
Sample solution is provided at 25 µL, 10mM.
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Description:
IC50: 0.013 μM
Transforming growth factor-β (TGF-β) belongs to the TGF-β superfamily, which consists of TGF-β1, TGF-β2, TGF-β3. TGF-β and its receptors are often chronically overexpressed in various human diseases, such as cancer, tissue fibrosis, inflammation, and autoimmunity. Therefore, blockade of TGF-β signaling pathway is an attractive target for drug development. Following TGF-β binding to the constitutively active type II receptor, the type I receptor (ALK5) is phosphorylated and creates a binding site for Smad2/Smad3 proteins, which are further phosphorylated. EW-7197 is a highly potent, selective inhibitor of TGF-β type I receptor kinase.
In vitro: EW-7197 inhibited ALK5 with IC50 value of 0.013 μM in a kinase assay and with IC50 values of 0.0165 and 0.0121 μM in HaCaT stable cells and 4T1 stable cells, respectively, in a luciferase assay. Selectivity profiling of EW-7197 using a panel of protein kinases revealed that it is a highly selective ALK5/ALK4 inhibitor [1].
In vivo: EW-7197 inhibited Smad/TGF-βsignaling, invasion, cell migration, and lung metastasis in MMTV/c-Neu mice and 4T1 orthotopic–grafted mice. EW-7197 inhibited the epithelial-to-mesenchymal transition in both TGF-β-treated breast cancer cells and 4T1 orthotopic–grafted mice as well[2].
Clinical trial: The First in human dose escalation study of EW-7197 in subjects with advanced stage solid tumors is ongoing [3].
Reference:
[1] Jin CH, Krishnaiah M, Sreenu D, Subrahmanyam VB, Rao KS, Lee HJ, Park SJ, Park HJ, Lee K, Sheen YY, Kim DK. Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl) -1H-imidazol-2-yl)methyl)-2-fluoroaniline (EW-7197): a highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent. J Med Chem. 2014 May 22;57(10):4213-38.
[2] Son JY, Park SY, Kim SJ, Lee SJ, Park SA, Kim MJ, Kim SW, Kim DK, Nam JS, Sheen YY. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther. 2014 Jul;13(7):1704-16. doi: 10.1158/1535-7163.MCT-13-0903. Epub 2014 May 9.
[3] https://clinicaltrials. gov/ct2/show/NCT02160106?term=EW-7197&rank=1
| Cell experiment [1,2]: | |
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Cell lines |
HaCaT (3TP-luc) and 4T1 (3TP-luc) stable cells, TGFβ-treated breast cancer cells |
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Preparation method |
Soluble in DMSO. 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. |
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Reacting condition |
96 hours |
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Applications |
In HaCaT (3TP-luc) and 4T1 (3TP-luc) stable cells, EW-7197 potently inhibited the TGF-β1-induced luciferase reporter activity with IC50 of 16.5 and 12.1 nM, respectively. EW-7197 inhibited TGFβ-induced Smad2 or Smad3 phosphorylation and the epithelial-to-mesenchymal transition (EMT) in TGFβ-treated breast cancer cells. EW-7197 abrogated TGFβ1-induced tumor cell migration and invasion in breast cells. |
| Animal experiment [2]: | |
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Animal models |
Mouse mammary tumor virus (MMTV)/c-Neu mice and 4T1 orthotopic–grafted mice |
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Dosage form |
intraperitoneal injection, 40 mg/kg, three times per week for 10 weeks |
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Application |
EW-7197 inhibited Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice and 4T1 orthotopic–grafted mice. EW-7197 inhibited the epithelial-to-mesenchymal transition (EMT) in 4T1 orthotopic–grafted mice. EW -7197 enhanced cytotoxic T lymphocyte activity in 4T1 orthotopic–grafted mice and increased the survival time of 4T1-Luc and 4T1 breast tumor–bearing mice. |
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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]. Son J Y, Park S Y, Kim S J, et al. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis[J]. Molecular cancer therapeutics, 2014, 13(7): 1704-1716. [2]. Jin C H, Krishnaiah M, Sreenu D, et al. Discovery of N-((4-([1, 2, 4] Triazolo [1, 5-a] pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1 H-imidazol-2-yl) methyl)-2-fluoroaniline (EW-7197): A Highly Potent, Selective, and Orally Bioavailable Inhibitor of TGF-β Type I Receptor Kinase as Cancer Immunotherapeutic/Antifibrotic Agent[J]. Journal of medicinal chemistry, 2014, 57(10): 4213-4238. |
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| Cas No. | 1352608-82-2 | SDF | |
| 别名 | Vactosertib，TEW-7197 | ||
| 化学名 | N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline | ||
| Canonical SMILES | CC1=NC(C2=C(N=C(N2)CNC3=CC=CC=C3F)C(C=C4)=CN5C4=NC=N5)=CC=C1 | ||
| 分子式 | C22H18FN7 | 分子量 | 399.42 |
| 溶解度 | ≥ 39.9mg/mL in DMSO | 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 | 2.5036 mL | 12.5182 mL | 25.0363 mL |
| 5 mM | 0.5007 mL | 2.5036 mL | 5.0073 mL |
| 10 mM | 0.2504 mL | 1.2518 mL | 2.5036 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