Selective inhibitor of TGF-β type I receptors ALK4 and ALK5 (IC50 values 129 nM and 47 nM, respectively). SB 505124 also inhibits the closely related ALK7 receptor, but not the BMP activated receptors (ALK1, 2, 3, and 6). It inhibits downstream TGF-β and Activin induced signaling of Smad2, but not BMP induced signaling of Smad1, -5, or -8. Pretreatment of the cells with SB-505124 blocked TGFβ–induced cell death but had no effect on TNFα–induced toxicity. Additionally, SB-505124 blocks activation of TGFβ induced MAPK pathways but is ineffective when these pathways are induced by EGF.