Sphingosine-1-phosphate (S1P) is an extracellular lipid mediator whose major effects are mediated through five distinct G protein-coupled receptors, S1P1/EDG-1, S1P2/EDG-5, S1P3/EDG-3, S1P4/EDG-6, and S1P5/EDG-8. S1P1 is important for vascular development and lymphocyte maturation, migration, and trafficking. CYM 5442 is a full agonist for S1P1 internalization, phosphorylation, and ubiquitination (EC50 = 1.35 nM). It is ineffective at S1P2, S1P3, S1P4, and S1P5 at concentrations up to 10 μM. CYM 5442 has been found to activate S1P1-mediated p42/p44 MAPK phosphorylation in CHO-K1 cells transfected with S1P1 with an EC50 value of 46 nM. At 50 nM, CYM 5442 can induce S1P1-dependent lymphopenia in mice, decreasing B and T cells by 65 and 85%, respectively.
