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