LY364947

Transforming growth factor-? (TGF-?) signals through a cell surface heteromeric complex involving type I (TGF-? RI) and type II (TGF-? RII) receptors. Downstream signal transduction is mediated by the TGF-? RI kinase domain through the phosphorylation of Smad proteins. LY364947 is a selective inhibitor of TGF-? RI (TGFR-I, T?R-I, ALK-5), with an IC50 value of 59 nM.{17263} LY364947 less effectively inhibits TGF-? RII (IC50 = 400 nM), p38 MAPK (IC50 = 740 nM), and mixed-lineage kinase 7 (MLK7; IC50 = 1,400 nM).{17263,17264} It inhibits TGF-?-induced cell growth (IC50 = 89 nM) in NIH 3T3 mouse fibroblasts{17263} and TGF-?-directed Smad phosphorylation, synthesis of fibronectin, PAI-1 and uPA protein, and matrigel invasion in MDA-MB-231 cells.{17265}