SAR247799 is a potent, selective G protein-biased S1P1 agonist with EC50 of 39 and 19 nM in β-arrestin and internalization assays, respectivey.
SAR247799 preferentially activated the Gi pathway, induced a concentration-dependent phosphorylation of extracellular-regulated kinase-1/2 (Erk1/2) and protein kinase B (Akt, EC50, 72.9 to 118 nM).
SAR247799 is inactive at S1P2, S1P3, and S1P5, and the EC50 value for S1P4 is >100-fold higher than that for S1P1 in inhibiting cAMP production.
SAR247799 induced phosphorylation of Ser1177 of endothelial nitric oxide synthase (eNOS) in a S1P1-dependent manner, indicating eNOS activation.
SAR247799 improved the microvascular hyperemic response without reducing lymphocyte numbers in a pig model of coronary endothelial damage.
