1352608-82-2

Basic information

• Product Name: EW-7197
• Synonyms: N-(2-fluorophenyl)-5-(6-methyl-2-pyridinyl)-4-[1,2,4]triazolo[1,5-a]pyridin-6-yl-1H-imidazole-2-methanamine;NOV-1301;TEW-7197;N-[[4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl]-2-fluoroaniline;CPD3325-A5;N-(2-Fluorophenyl)-5-(6-methyl-2-pyridinyl)-4-[1,2,4]triazolo-[1,5-a]pyridin-6-yl-1H-imidazole;1H-Imidazole-2-methanamine, N-(2-fluorophenyl)-5-(6-methyl-2-pyridinyl)-4-[1,2,4]triazolo[1,5-a]pyridin-6-yl-;Vactosertib
• CAS NO: 1352608-82-2
• Molecular Formula: C₂₂H₁₈FN₇
• Molecular Weight: 399.43
• Product Categories: Inhibitors
• Mol File: 1352608-82-2.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Density: 1.40±0.1 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 8.51±0.10(Predicted)
• CAS DataBase Reference: EW-7197(CAS DataBase Reference)
• NIST Chemistry Reference: EW-7197(1352608-82-2)
• EPA Substance Registry System: EW-7197(1352608-82-2)

Safety Data

• Hazardous Substances Data: 1352608-82-2(Hazardous Substances Data)

Usage

Description

EW-7197 is a novel ALK-5 kinase inhibitor and TGF-β Type I Receptor Kinase Inhibitor, which has demonstrated potent inhibition of breast to lung metastasis and various other cancer-related processes. It is a potential antitumor reagent with the ability to inhibit cell migration, invasion, and lung metastasis, as well as epithelial-to-mesenchymal transition (EMT) in TGF-β-treated breast cancer cells.

Uses

Used in Anticancer Applications:
EW-7197 is used as a TGF-β I receptor ALK4/ALK5 inhibitor for its highly potent, selective, and orally bioavailable properties. It blocks TGF-β/Smad signaling, cell migration, invasion, and lung metastasis in mouse mammary tumor virus/c-Neu mice and 4T1 orthotopic-grafted mice. Additionally, it inhibits the epithelial-to-mesenchymal transition (EMT) in both TGFβ-treated breast cancer cells and 4T1 orthotopic-grafted mice, enhancing cytotoxic T lymphocyte activity and increasing the survival time of 4T1-Luc and 4T1 breast tumor-bearing mice.
Used in Fibrosis Treatment:
EW-7197 is used as an inhibitor to block TGF-β/Smad and ROS signaling for the treatment of hepatic, renal, and pulmonary fibrosis. By inhibiting these signaling pathways, EW-7197 can potentially reduce the progression of fibrosis in these organs.
Used in Cancer and Fibrosis Research:
EW-7197 is used as a research tool to block TGF-β signaling and EMT in animal models of cancer and fibrosis. This allows scientists to study the effects of TGF-β inhibition on disease progression and develop new therapeutic strategies for cancer and fibrosis treatment.

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].

IC 50

0.013 μm

References

Park, S. A., et al. "EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-β/Smad and ROS signaling." Cellular & Molecular Life Sciences 72.10(2015):2023-2039. Kim, Min Jin, et al. "TGF-β Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1α-Induced Epithelial Mesenchymal Transition." Cellular Physiology & Biochemistry International Journal of Experimental Cellular Physiology Biochemistry & Pharmacology 38.2(2016):571. Son, J. Y., et al. "EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis." Molecular Cancer Therapeutics13.7(2014):1704.

Upstream product

• 614750-82-2 1-(6-methylpyridin-2-yl)-2-[1,2,4]triazolo-[1,5-a]pyridin-6-yl-ethanone 
• 356560-84-4 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione 
• 1352609-89-2 6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine 
• 1352609-91-6 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazole-2-carbaldehyde 

Downstream Products

• 1352610-25-3 N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline hydrochloride 

Relevant articles and documents

4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type i receptor kinase

A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2- yl)imidazoles and -pyrazoles 14a-c, 15a-c, 16a, 16b, 19a-d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC50 value of 0.018 μM and showed 95% inhibition at 0.03 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38α MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions.

2-pyridyl substituted imidazoles as therapeutic ALK5 and/or ALK4 inhibitors

This invention relates to 2-pyridyl substituted imidazoles which are inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and/or the activin type I receptor (ALK4), methods for their preparation, and their use in medicine, specifically in the treatment and prevention of a disease state mediated by these receptors.