SB 431542

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

SB 431542 is a known Src family kinase inhibitor that effectively blocks the transforming growth factor-β1-induced cell migration and invasion in both established and primary carcinoma cells. Potent TGF-beta inhibitor.

ChEBI: A member of the class of benzamides that is 4-(imidazol-2-yl)benzamide carrying additional 1,3-benzodioxol-5-yl and pyridin-2-yl substituents at positions 4 and 5 respectively on the imidazole ring.

A cell-permeable triarylimidazole compound that is shown to effectively inhibit cellular Smad2 phosphorylation (>90% inhibition by 10 μM inhibitor) upon vector-mediated expression of constitutively active ALK4, ALK5, or ALK7 in NIH 3T3 cells, while exhibiting little effect against Smad1 phosphorylation by other members of type I receptors for TGF-β in NIH 3T3 cultures expressing active ALK1, 2, 3, or 6. When tested directly in cell-free kinase assays, SB431542 is demonstrated to potently inhibit the activity of ALK4 and ALK5 (IC₅₀ = 140 nM and 94 nM, respectively) with no or much reduced potency toward a panel of 24 other kinases (IC₅₀ ≥10 μM in the presence of 10 μM ATP), including ALK2 and ALK6. Reported to improve the efficiency of 4-TF-induced human iPSCs generation from fibroblast cultures by >200-fold when used together with PD0325901 (Cat. No. 444966) and Thiazovivin (Cat. No. 420220).

Potent and selective inhibitor of the transforming growth factor- β (TGF- β ) type I receptor activin receptor-like kinase ALK5 (IC 50 = 94 nM), and its relatives ALK4 and ALK7. Suppresses TGF- β -induced proliferation of human osteosarcoma cells. Stimulates proliferation, differentiation and sheet formation of ESC-derived endothelial cells.

SB-431542 inhibits the TGF-β-mediated activation of SMAD proteins, expression of collagen and fibronectin, cell proliferation and cell motility. It does not inhibit kinases that are activated in response to serum or stress such as ERK, p38 or JNK.

Room temperature

SB431542 is a potent and selective ATP-competitive inhibitor of the transforming growth factor β1 activin receptor-like kinases -4, -5, and -7. Research studies using cell-free kinase assays show that SB431542 inhibits ALK4 and ALK5 with IC50 values of 140 nM and 94 nM, respectively, and ALK7 with slightly less potency. The SB431542 inhibitor displays a 100-fold greater selectivity for ALK5 than 25 other kinases, including p38 MAPK and JNK1. SB431542 inhibits Smad2 signaling induced by TGF-β and activin, but has no effect on BMP-induced Smad1 activation mediated by ALK -2, -3, and -6. Additional studies show that SB431542 enhances the proliferation and integrity of ESC-derived endothelial cells.

[1] N J LAPING. 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.[J]. Molecular Pharmacology, 2002, 62 1 1: 58-64. DOI:10.1124/mol.62.1.58
[2] GARETH J INMAN. 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.[J]. Molecular Pharmacology, 2002, 62 1 1: 65-74. DOI:10.1124/mol.62.1.65
[3] SHIGEO MATSUYAMA. SB-431542 and Gleevec inhibit transforming growth factor-beta-induced proliferation of human osteosarcoma cells.[J]. Cancer research, 2003, 63 22: 7791-7798.
[4] TETSURO WATABE. TGF-beta receptor kinase inhibitor enhances growth and integrity of embryonic stem cell-derived endothelial cells.[J]. Journal of Cell Biology, 2003, 163 6: 1303-1311. DOI:10.1083/jcb.200305147
[5] NANCY STANSLOWSKY. Functional differentiation of midbrain neurons from human cord blood-derived induced pluripotent stem cells.[J]. Stem Cell Research & Therapy, 2014, 5 2: 35. DOI:10.1186/scrt423