Latest research on FTY720

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

Latest findings

In contrast, the synthetic sphingosine analog of myriocin FTY720 leads to a specific down-regulation of proinflammatory signals while simultaneously inducing functional activity of CD4+CD25+ Treg [34]. [source, 2016]
FTY720 was suggested to offer a promising new therapeutic strategy for the treatment of IBD. [source, 2016]
Two recent studies using mouse models also divulged mechanisms, such as phosphorylation of sphingosine analog FTY720 and selective inhibition of SIN3 corepressor as novel strategies associated with the correction of epigenetic deregulation in ER-negative and TNBC leading to the restoration of Tamoxifen sensitivity. [source, 2016]
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]
FTY720 can also cross the blood-brain barrier, where it is then phosphorylated and likely regulates neuronal and glial cells [4, 5]. [source, 2016]
Siponimod (BAF312) ((E)-1- (4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carb oxylic acid)) is a S1PR1/S1PR5 dual agonist that has been developed by modification of the hydrophobic alkyl chain in FTY720 and replacement of the n-octyl moiety with a substituted benzyloxy oxime moiety [10]. [source, 2016]
Further replacement of an amino phosphate moiety of FTY720 by amino carboxylic acids has provided BAF312 with shorter elimination half-lives in vivo and with the added benefit of developing a ‘non’ pro-drug [16]. [source, 2016]
Some natural compounds, such as psoralidin and FTY720, or chemical compounds, such as non-steroidal anti-inflammatory drugs (NSAIDs) and tasquinimod, possess chemopreventive effects [5–8]. [source, 2015]
To resolve this, we treated dermatitis mice with the cell egress blockers FTY720 or 4-deoxypyridoxine (DOP), which retain cells in BM for 24 h2526, continuously from one day after transplantation of Luc-Tg Lin− cells, and monitored the increase in the luminescence signal in the inflamed ear (Fig. 4a). [source, 2015]
FTY720 treatment enhanced both the percentages and numbers of CD45.1+ cells in the BM, verifying the blockade of cell egress from BM during drug treatment. [source, 2015]