| Identification | Back Directory | [Name]
Acetic acid, 2-[4-[5-(3-chlorophenoxy)oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]- | [CAS]
1315311-14-8 | [Synonyms]
SAR247799
S1P1 agonist 3
Acetic acid, 2-[4-[5-(3-chlorophenoxy)oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy]- | [Molecular Formula]
C21H16ClN3O5 | [MOL File]
1315311-14-8.mol | [Molecular Weight]
425.82 |
| Chemical Properties | Back Directory | [Boiling point ]
618.9±65.0 °C(Predicted) | [density ]
1.412±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
3.07±0.10(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Description]
SAR247799 is a novel G-protein-biased sphingosine-1 phosphate receptor-1 (S1P1) agonist. | [Uses]
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]. | [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 (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 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. |
| [IC 50]
S1PR1: 12.6-493 nM (EC50) | [storage]
Store at -20°C | [References]
[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. DOI:10.1126/scisignal.aax8050
[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. DOI:10.1371/journal.pone.0257929
[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. DOI:10.1111/bcp.14632
[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 DOI:10.1111/bcp.14422 |
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