Vactosertib Hydrochloride (EW-7197 Hydrochloride) 是 TGFβRI (ALK5) 的小分子 ATP 竞争性抑制剂，其 IC50 值为 12.9 nM。
Vactosertib Hydrochloride (EW-7197 Hydrochloride) is a small-molecule ATP-competitive inhibitor of TGFβRI (ALK5) with an IC50 of 12.9 nM. IC50: 12.9 nM (ALK5)[1]
Kinase assays demonstrate that Vactosertib (EW-7197) is a small-molecule ATP-competitive inhibitor of TGFβRI (ALK5) with an IC50 of 12.9 nM. The IC50 values of Vactosertib against p38a is 1775 nM. Vactosertib also inhibits ACVR1B/ALK4 and the IC50 value against it is determined to be 17.3 nM. Vactosertib blocks the TGFβ-induced phosphorylation of Smad2 or Smad3 in a dose-dependent manner in 4T1 cells, and MDA-MB-231 cells. Vactosertib suppresses the TGFβ-induced nuclear translocation of Smad2/3 in 4T1 cells and MCF10A cells[1]. Vactosertib (EW-7197) treatment also dramatically reduces the colony-forming capacity of CML-MPPs in vitro in a dose-dependent manner[2].
Vactosertib (EW-7197; 40 mg/kg) treatment of MMTV/c-Neu transgenic mice significantly reduces lung metastasis by 60% compare with the control. Treatment with Vactosertib decreases the number of metastatic nodules compare with that in the Veh-treated control group by 53% and 68% (5 and 20 mg/kg). Vactosertib (0.625, 1.25, 2.5, or 5 mg/kg; five times/week) inhibits lung metastasis and increases the survival of 4T1-Luc cells, in a dose-dependent manner. Vactosertib also prolongs the survival of BALB/c mice orthotopically bearing 4T1 tumors by 36% at doses of 2.5 and 5 mg/kg[1].
[1]. Son JY, et al. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther. 2014 Jul;13(7):1704-16. [2]. Naka K, et al. Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells. Cancer Sci. 2016 Feb;107(2):140-8.
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