CYM50358 is a Potent and Selective S1PR4 Antagonist

Sphingosine-1 phosphate (S1P) is a signal sphingolipid, also known as a bioactive liposome. Specifically, S1P is an extracellular factor that acts as an effective lipid mediator by binding with specific receptor S1P receptors (S1PRs). Besides, S1P is a blood-derived liposome, especially in combination with lipoproteins such as high-density lipoprotein (HDL). Moreover, S1P is related to a variety of basic biological cell behaviors, including migration, adhesion, survival and proliferation, and physiological processes. Furthermore, S1PR1 is essential for the formation of platelets from megakaryocytes and their release from the bone marrow cavity into the circulation. S1P4 coupled with G α I and G α o proteins and activated ERK, MAPK, PLC cascade reactions. The change of the S1P4 subtype in the airway may effectively control the immunopathological response to viral infection. Meanwhile, S1P4 antagonists are suitable targets for reactive thrombocytosis. CYM50358 is a potent and selective S1PR4 antagonist.、

CYM50358 is a potent and selective S1PR4 antagonist.

How does CYM50358 work on the target? Let’s study it together. In the beginning, CYM50358 is a potent and selective S1PR4 antagonist, with an IC50 of 25 nM. Nonetheless, CYM50358 has the potential for the research of influenza infection.

In the second place, CYM50358 shows less potent inhibition of S1PR1 (IC50=6.4 μM). Nonetheless, CYM50358 (10 μM) has no effect on collagen-induced HSP27 phosphorylation. Particularly, it markedly reverses the suppressive effect of S1P on the collagen-induced phosphorylation of HSP27 (Ser-78). Obviously, the inhibitory effect of S1P on the phosphorylation of HSP27 is truly mediated through S1PR4 in human platelets.

All in all, CYM50358 is a potent and selective S1PR4 antagonist with anti-influenza infection activity.


Onuma T, et, al. Thromb Res. 2017 Aug;156:91-100.