FTY720 is a novel immune modulator that prolongs allograft transplant survival in numerous models by inhibiting lymphocyte emigration from lymphoid organs.[1] 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.[2] FTY720 (R)-phosphate is one of the stereoisomers of FTY720-phosphate, but it is apparently not formed in vivo.[3] FTY720 (S)-phosphate exhibits Ki values of 2.1, 5.9, 23, and 2.2 nM for S1P1,3,4,5, respectively, whereas the R isomer binds with 5 to130-fold lower affinity.[4]
Reference:
[1]. Brinkmann, V., Pinschewer, D.D., Feng, L., et al. FTY720: Altered lymphocyte traffic results in allograft protection. Transplantation 72(5), 764-769 (2001).
[2]. Brinkmann, V., Davis, M.D., Heise, C.E., et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem. 277(24), 21453-21457 (2002).
[3]. Albert, R., Hinterding, K., Brinkmann, V., et al. Novel immunomodulator FTY720 is phosphorylated in rats and humans to form a single stereoisomer. Identification, chemical proof, and biological characterization of the biologically active species and its enantiomer. Journal of Medicinal Chemistry 48, 5373-5377 (2005).
[4]. Kiuchi, M., Adachi, K., Tomatsu, A., et al. Asymmetric synthesis and biological evaluation of the enantiomeric isomers of the immunosuppressive FTY720-phosphate. Bioorganic & Medicinal Chemistry 13, 425-432 (2005).