Fingolimod-d4 is intended for use as an internal standard for the quantification of fingolimod by GC- or LC-MS. Fingolimod is a derivative of ISP-1 (myriocin), a fungal metabolite of the Chinese herb I. 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 Fingolimod 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 fingolimod results in defective egress of these cells from spleen, lymph nodes, and Peyer's patch.3 Fingolimod also enhances the activity of the sphingosine transporter Abcb1 and the leukotriene C4 transporter Abcc1 and inhibits cytosolic phospholipase A2 activity.4,5
1.Brinkmann, V., Pinschewer, D.D., Feng, L., et al.FTY720: Altered lymphocyte traffic results in allograft protectionTransplantation72(5)764-769(2001) 2.Brinkmann, V., Davis, M.D., Heise, C.E., et al.The immune modulator FTY720 targets sphingosine 1-phosphate receptorsJ. 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 1Nature427(6972)355-360(2004) 4.Honig, S.M., Fu, S., Mao, X., et al.FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodesJ. 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 receptorsBlood109(3)1077-1085(2007)