Sphingosine 1-Phosphate Receptor Antibodies

Sphingosine 1-phosphate (S1P) receptors are activated by the endogenous lipid sphingosine 1-phosphate. The receptors are designated as S1P1 through S1P5 receptors. S1P receptors, particularly S1P1, are expressed throughout all mammalian organ systems. Ligand delivery occurs via two known carriers: albumin and HDL-bound apolipoprotein M. Fingolimod (FTY720) binds as a phosphorylated metabolite to four of the five S1P receptors, and was the first oral therapy for multiple sclerosis (MS). Second-generation S1PR modulators siponimod, ozanimod, and ponesimod that target S1P1 and S1P5 are also FDA approved for the treatment of various MS forms. In 2021, ozanimod became the first S1P receptor modulator to be FDA approved for the treatment of ulcerative colitis. The mechanisms of action of fingolimod and other S1P receptor-modulating drugs now in development include binding S1P receptors in multiple organ systems, e.g., immune and nervous systems, although the precise nature of their receptor interactions requires further clarification.