SB-525334 (356559-20-1) is a potent and selective inhibitor of the transforming growth factor beta 1 receptor, activin receptor-like kinase (ALK5) (IC50 = 14.3 nM) and ALK4, (IC50 = 58.5 nM) with no activity at ALK2, 3 and 6.1. Blocks fibrosis markers and renal injury in the puromycin-induced nephritis model.1 SB-525334 causes significant attenuation in Smad2/3 nuclear translocation, decrease in CTGF-expressing cells, myofibroblast proliferation and type 1 collagen deposition resulting in an overall attenuation in bleomycin-induced pulmonary fibrosis.2 Sensitizes drug-resistant pancreatic cancer cells to gemcitabine3. Cell permeable and active in vivo.
1) Grygielko et al. (2005), Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis; J. Pharmacol. Exp. Ther., 313 943
2) Higashiyama et al. (2007), Inhibition of activin receptor-like kinase 5 attenuates bleomycin-induced pulmonary fibrosis; Exp. Mol. Pathol., 83 39
3) Kim et al. (2012), Transforming growth factor beta receptor I inhibitor sensitizes drug-resistant pancreatic cancer cells to gemcitabine; Anticancer Res., 32 799