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• 产品描述： 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

• 靶点： TGFBR1:2.5 nM (IC50);Smad3:10.4 nM (IC50);ALK;TGF-beta/Smad

• 体外研究：
  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.

• 体内研究：
  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: Pharmacokinetic Parameters of R-268712 in male WKY/Hos rats (n=4) 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/kgAdministration: 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.

• 参考文献：
  1. Terashima H, et al. Attenuation of pulmonary fibrosis in type I collagen-targeted reporter mice with ALK-5 inhibitors. Pulm Pharmacol Ther. 2019 Feb;54:31-38. 2. Terashima H, et al. R-268712, an orally active transforming growth factor-β type I receptor inhibitor, prevents glomerular sclerosis in a Thy1 nephritis model. Eur J Pharmacol. 2014 Jul 5;734:60-6. 3. Wang H, et al. Development of small molecule inhibitors targeting TGF-β ligand and receptor: Structures, mechanism, preclinical studies and clinical usage. Eur J Med Chem. 2020 Apr 1;191:112154.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.752 ml	13.759 ml	27.519 ml
  5 mM	0.55 ml	2.752 ml	5.504 ml
  10 mM	0.275 ml	1.376 ml	2.752 ml
  50 mM	0.055 ml	0.275 ml	0.55 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *