R-268712

R-268712 is an orally active and selective ALK-5 inhibitor, with an IC₅₀ of 2.5 nM. R-268712 inhibits the phosphorylation of Smad3 in a dose-dependent manner with an IC₅₀ of 10.4 nM. R-268712 suppresses glomerulonephritis as well as glomerulosclerosis by inhibiting TGF-β signaling, which can be used in studies of renal fibrosis and cancer^[1][2]. In Vitro: R-268712 (3, 10, 30, 100, 300 nM; 1 h) inhibits the phosphorylation of Smad3 in a dose-dependent manner with an IC₅₀ of 10.4 nM in HFL-1 cells^[1]. R-268712 (3, 10, 30, 100, 300 nM; 72 h) inhibits myofibroblast transdifferentiation (MTD) from fibroblasts in a dose-dependent manner without inhibition of cell growth in HFL-1cells^[1]. In Vivo: R-268712 (0.3, 1, 3, 10 mg/kg; p.o.; single) shows AUC_0-24 values of 0.075, 0.28, 1.6 and 8.2 μg•h/mL for dosages of 0.3, 1, 3, 10 mg/kg, respectively^[2].
R-268712 (1, 3, 10 mg/kg; p.o.; single daily for 3 days) inhibits renal luciferase activity in a dose-dependent manner in UUO model^[2].
R-268712 (0.3, 1 mg/kg; p.o.; single daily for 33 days) shows renoprotective effects (improves and maintains renal function as well as inhibits glomerular sclerosis) on Thy1 nephritis model when at dosage of 1 mg/kg^[2].