EW-7197

EW-7197 (Vactosertib, TEW-7197) is a highly potent, selective inhibitor of TGF-β type I receptor kinase (ALK5) with IC50 of 11 nM; also inhibits ALK4 (IC50=13 nM) and shows less potency for p38α (IC50=280 nM) ; exhibits no inhibition on ALK1/2/3/6 (>10 uM) ; inhibits Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice and 4T1 orthotopic-grafted mice; oral bioavailability (Hcl salt) .Blood Cancer Phase 1 Clinical (In Vitro) :Vactosertib (10-1000 nM; 30 minutes; 4T1 cells) treatment blocks the TGFβ-induced phosphorylation of Smad2 or Smad3 in a dose-dependent manner in 4T1 cells.Vactosertib suppresses the TGFβ-induced nuclear translocation of Smad2/3 in 4T1 cells and MCF10A cells. The IC50 value of Vactosertib on pSmad3 in 4T1 cells is 10-30 nM.Vactosertib abrogates TGFb1-induced tumor cell migration and invasion.TGFβ1 downregulated the mRNA level of CDH1 and upregulated the mRNA levels of FN1, HMGA2 (high-mobility group AT-hook 2), SNAI1, and SNAI2 (Snail family zinc finger 1 and 2, respectively) . Moreover, Vactosertib abolishes the TGFβ1-induced effects on genes related to epithelial-to-mesenchymal transition (EMT) . (In Vivo) :Vactosertib (40 mg/kg; intraperitoneal injection; every other day; for 10 weeks; MMTV/c-Neu female mice) treatment inhibits Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice.Vactosertib also inhibits the epithelial-to-mesenchymal transition (EMT) in both TGFβ-treated breast cancer cells and 4T1 orthotopic-grafted mice. Furthermore, Vactosertib enhances cytotoxic T lymphocyte activity in 4T1 orthotopic-grafted mice and increased the survival time of 4T1-Luc and 4T1 breast tumor-bearing mice.

1352608-82-2

Vactosertib | EW7197 | TEW-7197

>98% (HPLC)

10 mM in DMSO

FC1=CC=CC=C1NCC2=NC (C3=CN4C (C=C3) =NC=N4) =C (C5=NC (C) =CC=C5) N2

C22H18FN7

399.4236

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.