In vitro: In HaCaT (3TP-luc) and 4T1 (3TP-luc) stable cells, 12b potently inhibits the TGF-β1-induced luciferase reporter activity with IC50 of 16.5 and 12.1 nM, respectively. EW-7197 inhibits TGFβ-induced Smad2 or Smad3 phosphorylation and the epithelial-to-mesenchymal transition (EMT) in TGFβ-treated breast cancer cells. In addition, EW-7197 also abrogates TGFβ1-induced tumor cell migration and invasion in breast cells. In vivo: In rats, EW-7197 shows an oral bioavailability of 51% with high systemic exposure (AUC) of 1426 ng×h/mL and maximum plasma concentration (Cmax) of 1620 ng/mL. EW-7197 also shows low toxicity on the cardiovascular system, central nervous system, and respiratory system. In a mouse B16 melanoma model, EW-7197 (2.5 mg/kg daily p.o.) suppresses the progression of melanoma with enhanced cytotoxic T-lymphocyte (CTL) responses. EW-7197 enhances cytotoxic T lymphocyte activity in 4T1 orthotopic-grafted mice and increased the survival time of 4T1-Luc and 4T1 breast tumor-bearing mice.
|Cell lines||4T1 and MCF10A cells|
|Preparation method||Cells are seeded in 96 well plate and treated with indicated concentrations of EW-7197 in 0.2% HI-FBS medium for 72 h. Cells are dried after incubation with 10% TCA in media. Then, cells are incubated with 0.4% SRB (Sulforhodamine B) in 1% acetic acid for 30 min. After washing with 1% glacial acetic acid, bounded dye is released in 10 mM Tris buffer (pH 10.5) for 30 min. Absorbance is measured at 570 nm.|
|Incubation time||72 hours|
|Animal models||Mouse B16 melanoma model|
|Formulation||Artificial gastric fluid formulation (vehicle; ddH2O 900 mL, conc. HCl 7 mL, NaCl 2.0 g, pepsin 3.2 g).|
|Dosages||2.5 mg/kg daily|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||79 mg/mL in DMSO|
EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-β/Smad and ROS signaling.
Park SA, et al. Cell Mol Life Sci. 2015 May;72(10):2023-39. PMID: 25487606.
EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis.
Son JY, et al. Mol Cancer Ther. 2014 Jul;13(7):1704-16. PMID: 24817629.
|Related TGF-beta Products|
SD-208 is a selective TGF-βRI (ALK5) inhibitor with IC50 of 48 nM, >100-fold selectivity over TGF-βRII.
A 83-01 is a selective inhibitor of TGF-β type I receptor ALK5 kinase, type I activin/nodal receptor ALK4 and type I nodal receptor ALK7 (IC50 values are 12, 45 and 7.5 nM respectively).
A 77-01 is a potent inhibitor of TGF-β type I receptor superfamily activin-like kinase ALK5 with IC50 of 25 nM.
Kartogenin is an activator of the smad4/smad5 pathway, and promotes the selective differentiation of multipotent mesenchymal stem cells into chondrocytes.
Asiaticoside (Madecassol) is the active chemical component of the plant Centella asiatica.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.