Latest research on FTY720

Fingolimod is a sphingosine 1-phosphate receptor modulator indicated and approved for the treatment of relapsing-remitting multiple sclerosis.

FTY720 indications

The phosphorylated version of FTY720 (pFTY720) acts on four of the five S1PRs (S1PR1, S1PR3, S1PR4 and S1PR5) and acts as a functional antagonist at the S1PR1 subtype by causing S1PR1 internalisation, thereby inhibiting lymphocyte egress from lymph nodes to the periphery and central nervous system (CNS) [3]. [source, 2016]
Recently, FTY720 treatment was also shown to suppress tumor growth in a xenograft mice model of Ph(+) ALL cell lines, but not in that of Ph(−) ALL cells, showing selective effectiveness of FTY720 on tumor growth (Wallington-Beddoe et al., 2012). [source, 2015]
FTY720, an S1P analog, effectively inhibits the egress of T and B cells from lymph nodes (Kabashima et al., 2006; Matloubian et al., 2004), thereby reducing the number of antigen-primed/restimulated cells that recirculate to peripheral inflammatory tissues (Brinkmann and Lynch, 2002), and consequently halts inflammation. [source, 2015]
FTY720 treatment had no effect on renal lymphangiogenesis (Fig. 4A,B). [source, 2015]
FTY720 completely prevented α-SMA-positive myofibroblast accumulation at week 12 compared with non-treated proteinuric rats (Fig. 4G,H; P<0.05), but did not show any marked effect on collagen III deposition by immunohistochemistry (Fig. 4I,J). [source, 2015]
FTY720, an FDA-approved drug to treat multiple sclerosis, exerts different kinds of effects in the body (Halmer et al., 2014; Pitman et al., 2012). [source, 2015]
Several reports have shown the beneficial effect of FTY720 not only in a renal inflammatory reactions, but also in hampering renal profibrotic and fibrotic development, e.g. myofibroblast activation and collagen deposition (Shiohira et al., 2013; Ni et al., 2013a,b). [source, 2015]
By binding to the S1P1 receptor on LECs, FTY720 proved to be an effective drug in blocking lymphangiogenesis (Yin et al., 2011). [source, 2015]
In this current study, FTY720 treatment effectively reduced the number of lymphocytes in the blood circulation, and T cells in proteinuric kidneys, but did not have any impact on renal lymphangiogenesis. [source, 2015]
Interestingly, although FTY720 significantly prevented the increase of α-SMA-positive myofibroblasts, it was not effective in decreasing collagen III deposition, although it significantly reduced tubulointerstitial fibrosis (PAS scoring). [source, 2015]