FTY720 (S)-Phosphate

FTY720 is a novel immune modulator that prolongs allograft transplant survival in numerous models by inhibiting lymphocyte emigration from lymphoid organs.{11265} FTY720 is phosphorylated by sphingosine kinases in vivo, and then acts as a potent agonist at four of the five sphingosine-1-phosphate (S1P) receptors.{11284} FTY720 (S)-phosphate is the single stereoisomer formed by phosphorylation of FTY720 in vivo, as determined in rats and humans.{17113} It exhibits Ki values of 2.1, 5.9, 23, and 2.2 nM for S1P1,3,4,5, respectively, whereas the R enantiomer binds with 5 to 130-fold lower affinity.{17114} FTY720 (S)-phosphate causes internalization of S1P1 on lymphocytes, abrogating S1P-dependent egress of lymphocytes from lymphoid organs.{13737} It also enhances endothelial barrier function, stimulates the activity of the sphingosine transporter Abcb1 and the leukotriene C4 transporter Abcc1 and inhibits cytosolic phospholipase A2 activity.{13737},{11283},{14604}