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) |
| 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. |