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Chemical Structure| 1352608-82-2 同义名 : EW 7197;TEW-7197
CAS号 : 1352608-82-2
货号 : A287741
分子式 : C22H18FN7
纯度 : 99%+
分子量 : 399.424
MDL号 : MFCD28348363
存储条件：

Pure form Keep in dark place,Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(262.88 mM)，配合低频超声助溶，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：

IP 5%DMSO+40%PEG400+5% tween80+H2O 5 mg/mL clear

生物活性
靶点

  • TGFβRI/ALK5

    ALK5, IC50:11 nM

  • ALK4

    ALK4, IC50:13 nM
描述 EW-7197 is a potent and selective ALK5/ALK4 with IC50 values of 13nM/17nM. It inhibited cellular ALK5 activity with IC50 values of 16.5nM and 12.1nM measured by a luciferase assay in HaCaT (3TP-luc) stable cells and 4T1 (3TP-luc) stable cells, respectively[6]. EW-7197 dose-dependently reduced TGFβ1-induced Smad3 phosphorylation at concentration>30nM in 4T1 cells post 30min, and blocked Smad2/3 nuclear translocation at 1μM. Also it inhibited TGFβ1-induced 4T1 cell migration and invasion as well as inhibited EMT in breast cancer cells. Administration of EW-7197 at doses of 0.625, 1.25, 2.5 and 5mg/kg dose-dependently prolonged the life span of BALB/c 4T1 mice via inhibition of EMT. It inhibited metastasis and enhanced the activity of cytotoxic T lymphocytes in 4T1 orthotopic–grafted mice at dose of 20mg/kg[7].
作用机制 The [1,2,4]triazolo[1,5-a]pyridin-6-yl moiety of EW-7197 occupies the pocket for adenine ring of ATP and commonly forms a hydrogen bonding with NH of His283 in the backbone of hinge region of ALK5.[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
HEK293 cells Function assay Inhibition of human ERG channel expressed in HEK293 cells after 3 to 5.7 mins by whole-cell patch clamp technique, IC50=31.04 μM 24786585
human HaCaT cells Function assay 24 h Inhibition of ALK5 in human HaCaT cells assessed as inhibition of TGFbeta1-induced luciferase activity after 24 hrs by luciferase reporter gene assay, IC50=0.0165 μM 24786585
mouse 4T1 cells Function assay 24 h Inhibition of ALK5 in mouse 4T1 cells assessed as inhibition of TGFbeta1-induced luciferase activity after 24 hrs by luciferase reporter gene assay, IC50=0.0121 μM 24786585
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.50mL

0.50mL

0.25mL

12.52mL

2.50mL

1.25mL

25.04mL

5.01mL

2.50mL
参考文献

[1]Jin CH, Krishnaiah M, et al. 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, et al. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther. 2014 Jul;13(7):1704-16.

[3]Yoon JH, Jung SM, et al. Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes. EMBO Mol Med. 2013 Nov;5(11):1720-39.

[4]Jun EJ, Park JH, et al. EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus. Gastrointest Endosc. 2017 Jul;86(1):219-228.

[5]Naka K, Ishihara K, et al. Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells. Cancer Sci. 2016 Feb;107(2):140-8.

[6]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. doi: 10.1021/jm500115w. Epub 2014 May 13. PMID: 24786585.

[7]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. PMID: 24817629.