Vactosertib 是有效的、具有 ATP 竞争性的、具有口服活性的激活素受体样激酶 5 (ALK5) 抑制剂(IC50:12.9 nM)。它还以纳摩尔浓度抑制 ALK2 和 ALK4 (IC50为 17.3 nM)，表现出强大的抗转移活性和抗癌作用。

Vactosertib is an orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic 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. [1] 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. [3]

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. [1] 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. [2] 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. [3]

Protein Kinase Assay: A radioisotopic protein kinase assay (HotSpot assay) is performed at Reaction Biology Corporation.

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. (Only for Reference)

1352608-82-2

C22H18FN7

399.42

EW-7197;TEW-7197

Ethanol:40 mg/mL (100.1 mM)
H2O:<1 mgml
DMSO:73 mg/mL (182.8 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years