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 (S1P1,3,4,5) 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
Powered by Bioz1. 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.
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