Sphingosine-1-phosphate (S1P) is an extracellular lipid mediator whose major effects are mediated through four of the S1P receptors (S1P1/EDG-1, S1P2/EDG-5, S1P3/EDG-3, S1P4/EDG-6, and S1P5/EDG-8). Binding of S1P to S1P4 activates ERK, MAPK, and PLC downstream signal transduction pathways. ML-178 activates S1P4 with an EC50 value of 46.3 nM and is inactive against S1P1, S1P2, S1P3, and S1P5 (EC50s = >50 μM) and has no effect against a panel of additional receptors, transporters, and ion channels.
