Sphingosine 1 phosphate (S1P) is an endogenous ligand to a conserved family of five G-protein coupled receptors(S1P receptor subtype 1 -5), with effective concentrations (EC50) ranging from submicromolar to nanomolar levels [Chun, 2002]. Validation for a therapeutic approach targeting S1P receptors in autoimmune disease has been provided by the clinical development of FTY720 in MS (fingolimod; Novartis). GSK2018682 is an agonist at recombinant human S1P1 with some activity at S1P5 receptors but displays no agonist activity towards human S1P2, S1P3 or S1P4 up to a concentration of 10 µM. This selectivity is anticipated to minimise known cardiovascular effects mediated by S1P2/3 subtypes. Orally administered GSK2018682 is very effective in murine experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. GSK2018682 has been reasonably tolerated following single oral doses of 0.6mg to 24mg in an ongoing study (P1A114070) in healthy volunteers