product name EW-7197
Description: EW-7197 is a highly potent, selective, and orally bioavailable TGF-β receptor ALK4/ALK5 inhibitor with IC50 of 13 nM and 11 nM, respectively. EW-7197 showed potent in vivo anti-metastatic activity, indicating its potential for use as an anti-cancer therapy. EW-7197 inhibits TGF-β/Smad signaling and abrogates TGF-β1-induced tumor cell migration and invasion.
References: J Med Chem. 2014 May 22;57(10):4213-38; EMBO Mol Med. 2013 Nov;5(11):1720-39.
399.42
Formula
C22H18FN7
CAS No.
1352608-82-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 79 mg/mL (197.8 mM)
Water: <1 mg/mL
Ethanol: 43 mg/mL (107.7 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: A radioisotopic protein kinase assay (HotSpot assay) is performed at Reaction Biology Corporation. Cell Assay: 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. |
|---|---|
| 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. |
| Animal model | Mouse B16 melanoma model |
| Formulation & Dosage | Artificial gastric fluid formulation (vehicle; ddH2O 900 mL, conc. HCl 7 mL, NaCl 2.0 g, pepsin 3.2 g).; 2.5 mg/mL; p.o. |
| References | J Med Chem. 2014 May 22;57(10):4213-38; EMBO Mol Med. 2013 Nov;5(11):1720-39. |
