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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 FTY720 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 protection. Transplantation72764-769(2001).
2
Brinkmann, V., Davis, M.D., Heise, C.E., et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem277(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. Nature427355-360(2004).
4
Honig, S.M., Fu, S., Mao, X., et al. FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J Clin Invest111(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. Blood109(3)1077-1085(2007).
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SMILES
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CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1.Cl
Background Reading
Brinkmann, V., Pinschewer, D.D., Feng, L., et al. FTY720: Altered lymphocyte traffic results in allograft protection. Transplantation72764-769(2001).
Matloubian, M., Lo, C.G., Cinamon, G., et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature427355-360(2004).
Payne, S.G., Oskeritizian, C.A., Griffiths, R., et al. The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptors. Blood109(3)1077-1085(2007).
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 Invest111(5)627-637(2003).
Brinkmann, V., Davis, M.D., Heise, C.E., et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem277(24)21453-21457(2002).
What is recommended for IP injections of FTY720 in mice and are there any references?
For IP injections in mice, it is recommended to use the parent compound and not the phosphates or azido compounds. A Google Scholar search for "FTY720 in vivo" returned over 3,000 matches. From the first few articles it appears that FTY720 can be dissolved in various aqueous solutions including water, culture media, normal saline, and H2O:Me2SO (5:1 v/v). Some of these studies used oral gavage and IP injection.