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]
Vactosertib 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549 cells
0.5 µM
24 hours
To investigate the effect of Vactosertib on cell apoptosis, and the results indicated an increased rate of apoptosis.
Cancer Commun (Lond). 2024 Aug;44(8):884-888.
Human breast cancer cells
0.5 µM
24 hours
To investigate the effect of Vactosertib on breast cancer cell apoptosis, results showed significant increase in apoptosis
Diabetes Metab J. 2023 Jul;47(4):500-513.
MDA-MB-231 cells
1 µM
48 hours
To evaluate the effect of Vactosertib on cell proliferation, and the results showed significant inhibition of cell proliferation.
Cancer Commun (Lond). 2024 Aug;44(8):884-888.
Human pancreatic cancer cells
1 µM
48 hours
To evaluate the inhibitory effect of Vactosertib on pancreatic cancer cell proliferation, results showed significant reduction in cell proliferation
Diabetes Metab J. 2023 Jul;47(4):500-513.
Mouse osteosarcoma cells
0.79-2.1 µM
Inhibition of osteosarcoma cell growth
Cancer Commun (Lond). 2024 Aug;44(8):884-888.
Human osteosarcoma cells
0.79-2.1 µM
Inhibition of osteosarcoma cell growth
Cancer Commun (Lond). 2024 Aug;44(8):884-888.
AML12 mouse hepatocytes
0.5 µM
24 hours
EW-7197 improved TGF-β-induced cell morphological changes and reduced TGF-β-induced expression of α-SMA, Col I, and p-SMAD2/3.
Diabetes Metab J. 2023 Jul;47(4):500-513.
LX-2 human hepatic stellate cells
0.5 µM
24 hours
EW-7197 reduced TGF-β-induced expression of α-SMA, Col I, and p-SMAD2/3, indicating its anti-fibrotic effects.
Diabetes Metab J. 2023 Jul;47(4):500-513.
Panc02 murine pancreatic cancer cells
500 ng/ml
48 hours
Combination treatment of Vactosertib and T1-44 significantly inhibited TGF-β-induced cell migration
Cell Death Dis. 2023 Feb 10;14(2):93.
SNU2491 human pancreatic cancer cells
500 ng/ml
48 hours
Combination treatment of Vactosertib and T1-44 significantly inhibited TGF-β-induced cell migration
Cell Death Dis. 2023 Feb 10;14(2):93.
PDAC cells
80 µM
one week
To investigate the inhibitory effect of Vactosertib on TGF-β signaling pathway
J Exp Clin Cancer Res. 2022 Oct 26;41(1):315.
SAOS2 cells
0.1 µM
Regulation of gene expression, inhibition of osteosarcoma progression and metastasis
Cancer Commun (Lond). 2024 Aug;44(8):884-888.
Vactosertib 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Breast cancer xenograft model
Oral
50 mg/kg
Once daily for 21 days
To assess the effect of Vactosertib on tumor growth, and the results showed a significant reduction in tumor volume.
Cancer Commun (Lond). 2024 Aug;44(8):884-888.
BALB/c nude mice
Pancreatic cancer xenograft model
Oral
50 mg/kg
Once daily for 21 days
To evaluate the anti-tumor effect of Vactosertib in vivo, results showed significant reduction in tumor volume
Diabetes Metab J. 2023 Jul;47(4):500-513.
C57BL/6J mice
Non-alcoholic steatohepatitis (NASH) model
Oral
20 mg/kg
Once every 2 days for 6 weeks
Co-administration of EW-7197 and Cur5-8 alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score.
Diabetes Metab J. 2023 Jul;47(4):500-513.
C57BL/6 mice
Pancreatic cancer model
Oral
25 mg/kg
5 days a week for 4 weeks
Combination treatment of Vactosertib and T1-44 significantly reduced tumor growth and invasion, and improved survival in mice
Cell Death Dis. 2023 Feb 10;14(2):93.
Nude mice
Pancreatic cancer metastasis model
Intraperitoneal injection
40 mg/kg
Twice a week for three weeks
To evaluate the inhibitory effect of Vactosertib on pancreatic cancer metastasis, results showed that Vactosertib completely abrogated lung metastasis primarily originating from LAMC2-expressing cells.
J Exp Clin Cancer Res. 2022 Oct 26;41(1):315.
Nude mice
SAOS2 osteosarcoma model
Oral
50 mg/kg
5 days/week, duration not specified
Inhibition of osteosarcoma growth, reduction in tumor volume and metastasis
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
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