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. S1P4 couples to Gαi, Gαo, and Gα12/13 proteins leading to the stimulation of MAPK/ERK signaling pathways, as well as to PLC and Rho-Cdc42 activation, and is thought to contribute to immune responses. CYM 50308 is a novel agonist of SIP4 (EC50 = 56 nM) that displays 37-fold selectivity against S1P5 (EC50 = 2.1 μM) and no appreciable activity over the S1P1-3 subtypes at concentrations up to 25 μM.
