| 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. Phase 1.
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Targets
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| In vitro |
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]
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| 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. [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]
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COA
HPLC