SM16

Ki: ALK5 (10 nM), ALK4 (1.5 nM)

SM 16 inhibits TGFβ-induced plasminogen activator inhibitor-luciferase activity (IC ₅₀ =64 nM) and TGFβ- or activin-induced Smad2 phosphorylation at concentrations between 100 and 620 nM. SM 16 is tested against >60 related and unrelated kinases and shows moderate off-target activity only against Raf (IC ₅₀ =1 μM) and p38/SAPKa (IC ₅₀ =0.8 μM). SM 16 exhibits no inhibitory activity against ALK family members ALK1 and ALK6.

SM 16 penetrates tumor cells in vivo , suppressing tumor phosphorylated Smad2/3 levels for at least 3 h following treatment of tumor-bearing mice with a single i.p. bolus of 20 mg/kg SM 16. The growth of established AB12 tumors is significantly inhibited by 5 mg/kg/d SM 16 (P<0.001) delivered via s.c. miniosmotic pumps over 28 days.