SB-431542 (hydrate)

SB-431542 is a potent and selective inhibitor of the TGF-β1 receptor ALK5 (IC₅₀ = 94 nM)¹. It is a less potent antagonist of ALK4 (IC₅₀ = 140 nM)² and ALK7.³ It does not affect the BMP receptors ALK2, ALK3, ALK6, or a panel of other kinases tested.³ SB-431542 specifically blocks Smad signaling, reducing gene expression relevant to fibrosis and cancer.³ Through its effects on ALK/Smad signaling, SB-431542 suppresses renewal in embryonic and induced pluripotent stem cells and promotes their differentiation.^4,5

1.Callahan, J.F., Burgess, J.L., Fornwald, J.A., et al.Identification of novel inhibitors of the transforming growth factor ß1 (TGF-ß1) type 1 receptor (ALK5)Journal of Medicinal Chemistry45(5)999-1001(2002) 2.Laping, N.J., Grygielko, E., Mathur, A., et al.Inhibition of Transforming Growth Factor (TGF)-ß1-Induced Extracellular Matrix with a Novel Inhibitor of the TGF-ß Type I Receptor Kinase Activity: SB-431542Molecular Pharmacology62(1)58-64(2002) 3.Inman, G.J., NicolÁs, F.J., Callahan, J.F., et al.SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7Molecular Pharmacology62(1)65-74(2002) 4.James, D., Levine, A.J., Besser, D., et al.TGFß/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cellsDevelopment1321273-1282(2005) 5.Chambers, S.M., Fasano, C.A., Papapetrou, E.P., et al.Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signalingNature Biotechnology27(3)275-280(2009)