SAR247799 T38716

Product Introduction
Bioactivity


英文名: SAR247799

描述: SAR247799 (S1P1 agonist 3) is an orally-active, selective G-protein-biased agonist for the sphingosine-1 phosphate receptor-1 (S1P1). It demonstrates EC50 values ranging from 12.6 to 493 nM in S1P1-overexpressing cells and HUVECs. SAR247799 holds promise as a valuable tool for investigating endothelial protection, particularly in the context of type-2 diabetes and metabolic syndrome[4].

体外活性: SAR247799 (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10 μM; 10 min) induces a concentration-dependent phosphorylation of extracellular-regulated kinase-1/2 (Erk1/2) and protein kinase B (Akt) in HUVECs[1]. SAR247799 (0-10 μM, 8 min) induces impedance change in HUVECs in a dose-dependent manner[1]. SAR247799 (1 μM, 1st) does not cause desensitization demonstrated by Ca 2+ flux assay in S1P1-Chinese hamster ovary (CHO) cells[1].

体内活性: SAR247799 (1 and 3 mg/kg; p.o.; 1 h before renal occlusion) dose dependently reduces the severity of ischemia/reperfusion (I/R)–induced acute kidney injury[1]. SAR247799 (0.3, 1, 3 mg/kg; i.v.) dose dependently increases the coronary conductance ratio in pig model of coronary endothelial dysfunction[1]. SAR247799 (30-min intravenous administration; 8- to 10-week-old farm pig) exposure (C max and AUC) increases with dose in pigs. Pharmacokinetic parameters[1]: Dose (mg/kg) N C max (g/mL) T max (h) T last (h) AUC 0-last (g.h/mL) Cl (L/h/kg) Vss (L/kg) T 1/2z (h) 1 4 2.08 (8) 0.5 [0.5] [8-48] 11.8 (46) 0.113 (75) 0.516 (11) 5.62 (57) 3 7 8.10 (12) 0.5 [0.5] [24-72] 42.2 (23) 0.0754 (30) 0.446 (16) 6.21 (28) 10 3 36.7 (5) 0.5 [0.5-0.75] 72 294 (13) 0.0343 (13) 0.338 (7) 7.73 (8) 30 6 112 (27) 0.5 [0.5- 1.0] [48-72] 908 (16) 0.0338 (18) 0.294 (11) 7.35 (11) Mean values with (CV%) except T max , which is expressed as median value with [range] and Tlast as [range]. C max , maximum concentration. T max , time at which maximum concentration achieved. T last , last time point sampled. AUC 0-last , area under curve from 0 to last time point. Cl, clearance. Vss, volume at steady state or volume of distribution. T 1/2z , elimination half-life. N, number of animals. Animal Model: Acute kidney injury rats (12 to 15-week-old Fischer rats)[1]Dosage: 1 and 3 mg/kg Administration: P.o.; administered 1 hour before renal occlusion. Result: Inhibited the increase in serum creatinine (89 and 96% at 1 and 3 mg/kg) and urea (61 and 85% at 1 and 3 mg/kg). Protected renal proximal tubules against necrosis and blunted the development of interstitial hemorrhage. Animal Model: Acute kidney injury rats (8- to 12-week-old Fischer rats)[1]Dosage: 3 mg/kg Administration: P.o.; twice a day for 7 days and twice a day for 7 day Result: Showed a dosedependent trend for reducing macrophage.

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

关键字: SAR 247799 | SAR-247799

SAR247799 T38716信息由TargetMol中国为您提供，如您想了解更多关于SAR247799 T38716报价、型号、参数等信息，欢迎来电或留言咨询。

注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途