FTY720 (S)-Phosphate

FTY720 (S)-phosphate is the single stereoisomer formed by phosphorylation of FTY720 in vivo, as determined in rats and humans.¹ It exhibits K_i 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.² FTY720 (S)-phosphate causes internalization of S1P₁ on lymphocytes, abrogating S1P-dependent egress of lymphocytes from lymphoid organs.³ 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.³,⁴,⁵

WARNING This product is not for human or veterinary use.

1. 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. J. Med. Chem. 48(16), 5373-5377 (2005).

2. Kiuchi, M., Adachi, K., Tomatsu, A., et al. Asymmetric synthesis and biological evaluation of the enantiomeric isomers of the immunosuppressive FTY720-phosphate. Bioorg. Med. Chem. 13(2), 425-432 (2005).

3. Brinkmann, V. FTY720: Mechanism of action and potential benefit in organ transplantation. Yonsei Med. J. 45(6), 991-997 (2004).

4. Honig, S.M., Fu, S., Mao, X., et al. FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J. Clin. Invest. 111(5), 627-637 (2003).

5. Payne, S.G., Oskeritizian, C.A., Griffiths, R., et al. The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A₂ independently of sphingosine-1-phosphate receptors. Blood 109(3), 1077-1085 (2007).