SAR247799

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SAR247799

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

1315311-14-8

S1P1 agonist 3

SAR247799 (S1P1 agonist 3) 是一种具有口服活性的，选择性 G 蛋白偏向的鞘氨醇-1 磷酸受体-1 (S1P1) 激动剂，在 S1P1 过表达细胞和 HUVEC 中的 EC₅₀为 12.6-493 nM。SAR247799 可用于内皮保护的研究，包括 2 型糖尿病、代谢综合征。

生物活性

SAR247799 (S1P1 agonist 3) is an oral activity, selective G-protein-biasedsphingosine-1 phosphate receptor-1 (S1P1 )agonist, with EC₅₀s rang from 12.6 to 493 nM in S1P1-overexpressing cells and HUVECs. SAR247799 can be used for the research of endothelial protection, including type-2 diabetes, metabolic syndrome^[1]^[2]^[3]^[4].

IC₅₀& Target^[1]

S1PR1

12.6-493 nM (EC₅₀)

体外研究
(In Vitro)

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 Ca²⁺flux assay in S1P1-Chinese hamster ovary (CHO) cells^[1].

体内研究
(In Vivo)

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_maxand 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.

Clinical Trial

分子量

425.82

性状

Solid

Formula

C₂₁H₁₆ClN₃O₅

CAS 号

1315311-14-8

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

溶解性数据

In Vitro:

DMSO : 33.33 mg/mL(78.27 mM;Need ultrasonic)

配制储备液

浓度溶剂体积质量

1 mg

5 mg

10 mg

1 mM	2.3484 mL	11.7421 mL	23.4841 mL
5 mM	0.4697 mL	2.3484 mL	4.6968 mL
10 mM	0.2348 mL	1.1742 mL	2.3484 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture and light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。