R-268712

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

R-268712 是一种有效、选择性、口服活性的 TGF-β I 型受体 ALK5 抑制剂，IC50 为 2.5 nM。

R-268712 is a potent, selective, orally active inhibitor of TGF-β type I receptor ALK5 with IC50 of 2.5 nM, >5,000-fold more selectivity than p38 MAPK; inhibits the development of renal fibrosis in a dose-dependent manner in a unilateral ureteral obstruction (UUO) model at doses of 1, 3 and 10mg/kg, also reduces proteinuria and glomerulosclerosis significantly with improvement of renal function in glomerulonephritis models.

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.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. Cell Viability Assay Cell Line:HFL-1 cells Concentration:3, 10, 30, 100, 300 nM Incubation Time:1 or 72 h Result:Inhibited the phosphorylation of Smad3 in a dose-dependent manner with an IC50 of 10.4 nM when incubation 1 h.Suppressed myofibroblast transdifferentiation (MTD) from fibroblasts in a dose-dependent manner without inhibition of cell growth when incubation after 72 h.

R-268712 (0.3, 1, 3, 10 mg/kg; p.o.; single) shows AUC0-24 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.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.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. Animal Model:Male WKY/Hos rats.Dosage:0.3, 1, 3, and 10 mg/kg Administration:Oral administration; single.Result:Animal Model:Male Col1a1-Luc Tg rats (10 to14-week-old; UUO model; n=5-6).Dosage:1, 3, 10 mg/kg Administration:Oral administration; single daily for 3 days.Result:Suppressed activity of renal luciferase in a dose-dependent manner.Animal Model:Male WKY/Hos rats (4-week-old; Thy1 nephritis model; n=7).Dosage:0.3, 1 mg/kg Administration:Oral administration; single daily for 33 days.Result:Significantly reduced proteinuria at day 21( the repression continued until day 28), and serum creatinine level (dosage at 1 mg/kg).Apparently suppressed glomerular sclerosis by 28% and reduced the increase of the hydroxyproline content when at 1 mg/kg.Suppressed the activation of mesangial parenchymal cell and the injury of podocyte on the basis of TGF-β signaling inhibition at 1 mg/kg.

R268712 | R 268712

TGF-beta/Smad

TGFBR

TGFBR

Cancer

——

879487-87-3

363.3882

C20H18FN5O

>98% (HPLC)

10 mM in DMSO

CC1=CC=CC(C2=NNC=C2C3=CC=C(F)C(C4=CN(CCO)N=C4)=C3)=N1

1H-Pyrazole-1-ethanol, 4-[2-fluoro-5-[3-(6-methyl-2-pyridinyl)-1H-pyrazol-4-yl]phenyl]-

(-20℃)

With Ice Pack

≥ 2 years