Targeting S1P signaling for drug development.

Sphingosine-1-phosphate (S1P), a downstream metabolite of the sphingolipid pathway, exerts diverse biological functions, is implicated in a wide spectrum of diseases, and has been shown to have central roles in regulating cell proliferation, migration, and immune cell trafficking. Five agonists of its receptor have been approved for the treatment of multiple sclerosis, and an inhibitor targeting its production is currently undergoing clinical trials for cancer therapy. Here, we discuss the modulators and their preliminary structure-activity relationships in terms of the generation, transportation, and degradation of S1P.