Sphingosine-1-phosphate ( S1P ), the bioactive sphingolipid metabolite, is a critical regulator of many physiological and pathophysiological processes, including cancer, atherosclerosis, diabetes and osteoporosis. S1P and its receptors (S1P1-5) play critical roles in many pathologic processes, including cancer. S1P/sphingosine-1-phosphate receptor (S1PR) axis plays critical role in a wide variety of physiologic and pathophysiological processes in cancer. S1P2 is a potential mediator of otoprotection. S1P2 may serve as a therapeutic target for attenuating cisplatin-mediated ototoxicity.

JTE-013 is a known specific S1P2 antagonist. JTE-013 inhibits the specific binding of radiolabeled S1P to membranes of Chinese hamster ovary cells transfected with human and rat S1P2, with IC₅₀ values of 17 nM and 22 nM. Moreover, JTE-013 alone produces a significant increase in excitability in a time- and concentration-dependent manner in 70-80% of recorded neurons. JTE-013 is capable of increasing excitability via a mechanism that is dependent on G protein activation. JTE-013 blocks the binding of S1P to S1PR2 expressed in CHO cells with an IC₅₀ of ∼20 nM. However, JTE-013 has little to no effect on S1P binding to either S1PR1 or S1PR3 even at concentrations up to 10 μM.

JTE-013 inhibits not only S1P-induced vasoconstriction but also vasoconstriction induced by KCl, the prostanoid analog U46619, and endothelin-1. JTE-013 inhibits C-C motif ligand 2 expression and is able to significantly inhibit subsequent tumor-associated macrophage infiltration in neuroblastoma xenografts. In addition, JTE-013 may be unstable in vivo and is rapidly metabolized in liver microsomes. All in all, JTE-013 is a specific, potent, and stable S1P2 antagonist for potential clinical and experimental use.