Sphingosine-1-phosphate receptor 1 (S1P₁) is one of five high affinity G protein-coupled S1P receptors which mediate a variety of effects including lymphocyte recirculation in the blood.¹ Non-selective S1P receptor agonists, such as FTY720, produce clinical immunosuppression useful for preventing transplant rejection and treating autoimmune diseases. However, they also cause bradycardia by activating S1P₃, the receptor responsible for regulation of heart rate.² SEW2871 is a selective S1P₁ receptor agonist in both human and mouse that is not active at the S1P_2-5 receptors. SEW2871, therefore, suppresses the immune response by decreasing the number of lymphocytes circulating in blood without causing bradycardia.²

1 Kluk, M.J., Hla, T. Signaling of sphingosine-1-phosphate via the S1P/EDG-family of G-protein-coupled receptors. Biochim Biophys Acta 1582 72-80 (2002).

2 Sanna, M.G., Liao, J., Jo, E., et al. Sphingosine 1-phosphate (S1P) receptor subtypes SIP₁ and SIP₃, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem 279(14) 13839-13848 (2004).

Sanna, M.G., Liao, J., Jo, E., et al. Sphingosine 1-phosphate (S1P) receptor subtypes SIP₁ and SIP₃, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem 279(14) 13839-13848 (2004).

Kluk, M.J., Hla, T. Signaling of sphingosine-1-phosphate via the S1P/EDG-family of G-protein-coupled receptors. Biochim Biophys Acta 1582 72-80 (2002).

SEW2871 is available in the following screening library:

• Bio-active Lipid I Screening Library (96-Well)