W123

W123, an analog of FTY720, is a competitive antagonist of sphingosine-1-phosphate (S1P) type 1 receptor (S1P1), which is measured by GTPγS activation, cell migration, ligand-induced receptor internalization, and mitogen-activated protein kinase recruitment.

S1P plays a vital role in the entire human body, involving in mediating skin, vascular endothelial, and immune cells. S1P1, also known as EDG-1, is one of the five high affinity G protein-coupled S1P receptors and mediates lymphoid, endothelial, and neuronal cell responses to S1P.

In vitro: W123 reversed the effects of S1P1 agonists, FTY720, p-FTY720, and SEW2871. Superoxide dismutase and catalase activity level seen in W123-treated groups were reversely improved via antagonizing the S1P receptor induced by W123. W123 reduced phosphorylated levels of PI3K, Akt, and FoxO3a in different ways, indicating that the activation of S1P1 receptor in the context of oxidative stress elicited the phosphorylation/activation of PI3K/Akt and thus the phosphorylation/inactivation of FoxO3a which in turn promoted PC12 cell survival [1].

In vivo: Up to now, in vivo study of W123 is still in the development stage.

Reference:
[1].  Safarian, F., Khallaghi, B., Ahmadiani, A., & Dargahi, L. Activation of S1P1 Receptor Regulates PI3K/Akt/FoxO3a Pathway in Response to Oxidative Stress in PC12 Cells. Journal of Molecular Neuroscience. 2014; 56(1): 177-187.