EW-7197

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

EW-7197 (Vactosertib, TEW-7197) 是一种高效、选择性的 TGF-β I 型受体激酶 (ALK5) 抑制剂，IC50 为 11 nM。

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.

Western Blot Analysis Cell Line:4T1 cells Concentration:10 nM, 30 μM, 50 nM, 100 μM, 300 nM, 500 nM, 1000 nM.Incubation Time:30 minutes Result:Blocked the TGFb-induced phosphorylation of Smad2 or Smad3 in a dose-dependent manner.

Animal Model:Mammary tumor virus (MMTV)/c-Neu female mice (32-week-old) Dosage:40 mg/kg Administration:Intraperitoneal injection; every other day; for 10 weeks Result:Inhibited Smad/TGFβ signaling, cell migration, invasion, and lung metastasis in MMTV/c-Neu mice.

Vactosertib | EW7197 | TEW-7197

TGF-beta/Smad

TGFBR

ALK1|ALK2|ALK3|ALK4|ALK5

Cancer

Blood cancer

1352608-82-2

399.4236

C22H18FN7

>98% (HPLC)

10 mM in DMSO

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

1H-Imidazole-2-methanamine,N-(2-fluorophenyl)-5-(6-methyl-2-pyridinyl)-4-[1,2,4]triazolo[1,5-a]pyridin-6-yl-

(-20℃)

With Ice Pack

≥ 2 years