SIS3

Selective Smad3 inhibitor; attenuates TGF-β1-dependent Smad3 phosphorylation and Dna binding. Has no effect on Smad2, p38 MAPK, ERK or PI 3-kinase signaling. Inhibits TGF-β1-induced myofibroblast differentiation of dermal fibroblasts. Also inhibits TGF-β2-induced endothelial cell differentiation in iPSCs. (In Vitro) : (E) -SIS3 (0.3-10 μM; for 1 hour) attenuates the TGF-beta1-induced phosphorylation of Smad3 and interaction of Smad3 with Smad4. (E) -SIS3 (0.1 , 10, 50 μM; 30 min) significantly suppresses the expression of FN and α-SMA, but not that of Sphk2 provoked by TGF-β1. (E) -SIS3 (10 μM; 24 hours) significantly reduces both α-SMA and palladin expression that is enhanced by TWEAK in Primary human dermal fibroblasts. (E) -SIS3 significantly inhibits L4 development at five concentrations from as low as 2 μM to 50 μM (5 μM, 10 μM, 20 μM and 50 μM) in a dose-dependent manner.