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FTY720 is a derivative of ISP-1 (myriocin), a fungal metabolite of the Chinese herb Iscaria sinclarii as well as a structural analog of sphingosine. It 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 kinase, which then acts as a potent agonist at four of the sphingosine-1-phosphate (S1P) receptors (S1P1, S1P3, S1P4, and S1P5).2 Down-regulation of S1P1 receptors on T and B lymphocytes by FTY720 results in defective egress of these cells from spleen, lymph nodes, and Peyer’s patch.3 azido-FTY720 is a highly photoreactive analog of FTY720 that can be used to identify receptor binding sites for this ligand.4
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1
Brinkmann, V., Pinschewer, D.D., Feng, L., et al. FTY720: Altered lymphocyte traffic results in allograft protection. Transplantation 72 764-769 (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
Matloubian, M., Lo, C.G., Cinamon, G., et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427 355-360 (2004).
4
Sun, C., Bittman, R. A photoreactive analogue of the immunosuppressant FTY720. J Org Chem 71 2200-2202 (2006).
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