(S)-FTY720 Phosphate

FTY720P is the bioactive form of the novel immunosuppressive drug fingolimod (FTY720). FTY720 is converted to FTY720P by sphingosine kinase and the (S)-isomer acts as an agonist to four S1P receptors (S1P_1,3,4,5) with IC₅₀s of 2.1, 5.9, 23 and 2.2 nM respectively. The R isomer binds with 5-10 fold lower affinity. FTY720P improves the survival of neonatal rat oligodendrocytes, regulates oligodendrocyte progenitor cells differentiation, promotes astrocyte migration via extracellular signal-regulated kinase (ERK) signaling. Recently published results indicate involvement of FTY720P in complete viral clearance of persistent infection caused by clone 13 of lymphotic choriomeningitis virus (LCMV).

Publications

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1. Bucki, R., et al. (2010). “Plasma gelsolin modulates cellular response to sphingosine 1-phosphate.” Am J Physiol Cell Physiol 299(6): C1516-1523.
2. Gu, Y., et al. (2011). “Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway.” The Journal of Cell Biology 193(4): 667-676.
3. Trkov, S., et al. (2012). “Fingolimod—A sphingosine-like molecule inhibits vesicle mobility and secretion in astrocytes.” Glia 60(9): 1406.
4. Samuvel, D. J., et al. (2015). “AKP-11 – A Novel S1P1 Agonist with Favorable Safety Profile Attenuates Experimental Autoimmune Encephalomyelitis in Rat Model of Multiple Sclerosis.” PLoS ONE 10(10): e0141781.
5. Bar-Ephraim, Y. E., et al. (2019). “CD62L Is a Functional and Phenotypic Marker for Circulating Innate Lymphoid Cell Precursors.” The Journal of Immunology 202(1): 171-182.