Background:

SB525334 is a potent inhibitor of transforming growth factor-beta1 (TGF-beta1) receptor, activin receptor-like kinase (ALK5). It specifically inhibits ALK5 with IC50 value of 14.3nM, which shows 4-fold higher potency against ALK4 [1].

SB525334 has been demonstrated to reduce smad2/3 nuclear fluorescence induced by TGF-beta1 in human renal proximal tubule epithelial (RPTE) cells. Additionally, SB525334 inhibits TGF-beta1 mediated procollagen and PAI-1 expression in human renal carcinoma cells A498 [1].

SB525334 dose-dependently reduces Urinary protein, procollagen alpha1(I) mRNA and procollagen alpha1(III) mRNA when administered orally in acute puromycin aminonucleoside (PAN) rat model of renal disease [1].

Reference:
[1] Grygielko ET1, Martin WM, Tweed C, Thornton P, Harling J, Brooks DP, Laping NJ.  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. 2005 Jun;313(3):943-51.