SB431542, Free Base

Soluble in DMSO. SB-431542 selectively inhibited Smad3 phosphorylation, with an IC50 of 94 nM. It also blocked TGF-beta1-induced nuclear Smad3 localization. Laping N.J., et al. 'Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB-431542.' Mol. Pharmacol. 62: 58-64 (2002). SB-431542 is a potent inhibitor of activin receptor-like kinase (ALK)5 (the TGF-beta type I receptor). It also inhibits the activin type I receptor ALK4 and the nodal type I receptor ALK7. It has no major effect on the other ALK family members that recognize bone morphogenetic proteins (BMPs). Inman G.J., et al. 'SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7.' Mol. Pharmacol. 62: 65-74 (2002). SB-431542 is a specific inhibitor of TGF-beta receptor kinase. It inhibits TGF-beta-induced transcription, gene expression and tumor-promoting effects. Interestingly, SB-431542 promoted anchorage independent growth of cells which were growth-inhibited by TGF-beta, whereas it inhibited colony formation by cells which were growth-promoted by TGF-beta. Halder S.K., et al. 'A specific inhibitor of TGF-beta receptor kinase, SB-431542, as a potent antitumor agent for human cancers.' Neoplasia. 7: 509-521 (2005).