For research use only. Not for therapeutic Use.
SAR247799 (S1P1 agonist 3) is an oral activity, selective G-protein-biased sphingosine-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].
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].
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 (Cmax and AUC) increases with dose in pigs. Pharmacokinetic parameters [1]:
Dose (mg/kg)
N
Cmax (g/mL)
Tmax (h)
Tlast (h)
AUC0-last (g.h/mL)
Cl (L/h/kg)
Vss (L/kg)
T1/2z (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 Tmax, which is expressed as median value with [range] and Tlast as [range]. Cmax, maximum concentration. Tmax, time at which maximum concentration achieved. Tlast, last time point sampled. AUC0-last, area under curve from 0 to last time point. Cl, clearance. Vss, volume at steady state or volume of distribution. T1/2z, elimination half-life. N, number of animals.
| Catalog Number | I045562 |
| CAS Number | 1315311-14-8 |
| Synonyms | 2-[4-[5-(3-chlorophenoxy)-[1,3]oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]acetic acid |
| Molecular Formula | C21H16ClN3O5 |
| Purity | ≥95% |
| InChI | InChI=1S/C21H16ClN3O5/c1-11-6-13(7-12(2)18(11)28-10-17(26)27)19-24-16-9-23-21(25-20(16)30-19)29-15-5-3-4-14(22)8-15/h3-9H,10H2,1-2H3,(H,26,27) |
| InChIKey | WRBZNIUFAKIIQG-UHFFFAOYSA-N |
| SMILES | CC1=CC(=CC(=C1OCC(=O)O)C)C2=NC3=CN=C(N=C3O2)OC4=CC(=CC=C4)Cl |
| Reference | [1]. Poirier B, et al. A G protein-biased S1P1 agonist, SAR247799, protects endothelial cells without affecting lymphocyte numbers. Sci Signal. 2020 Jun 2;13(634):eaax8050. [2]. Evaristi MF, et al. A G-protein-biased S1P1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome. PLoS One. 2022 Jan 14;17(1):e0257929. [3]. Bergougnan L, et al. Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial. Br J Clin Pharmacol. 2021 May;87(5):2303-2320. [4]. Bergougnan L, et al. First-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral doses of SAR247799, a selective G-protein-biased sphingosine-1 phosphate receptor-1 agonist for endothelial protection |
