Ozanimod (RPC-1063) is a Selective S1P1 and S1P5 Receptor Agonist

Sphingosine 1-phosphate (S1P) is a lysophosphatidic mediator, which can activate G protein-coupled sphingosine 1-phosphate receptor. Specifically, this leads to a variety of cellular and tissue responses, including lymphocyte transport, endothelial development, integrity, and maturation. Besides, S1P1 is one of the most abundant and widely expressed members of GPCR superfamily. S1P, the ligand of S1P1, is produced during sphingolipid metabolism. Moreover, S1P is into extracellular space through specific and extensively specific lipid transporters. The function of the S1P receptor in maintaining and regulating biological barrier activity has profound biological significance. Furthermore, S1PRs is widely in many cell types, including immune, cardiovascular and central nervous system.

Among the five known high-affinity S1P receptors, S1P1 receptor subtype is the most common in various cell types. Meanwhile, studies on S1P deletion have revealed its essential endothelial function in the migration of arterial smooth muscle cells. Nonetheless, S1P5 affects proliferation and migration and has recently related to early TGF- β The process of induction. Extracellular S1P was distributed in circulating blood and lymph in micromolar and high nanomolar concentrations, respectively. In cancer models, S1P1 activation is relevant to persistent STAT3 activation and inflammation that promotes tumorigenesis. In preclinical disease models and clinical studies, the efficacy of targeting the S1P receptor for the treatment of autoimmune diseases has been fully established. Today, we will introduce a selective S1P1 and S1P5 receptor agonist, Ozanimod.

Ozanimod (RPC-1063) is a Selective S1P1 and S1P5 Receptor Agonist.

Above all, Ozanimod (RPC-1063) is a potent and selective S1P1 and S1P5 receptor agonist.  Importantly, Ozanimod has EC50s of 410 pM and 11 nM in [35S]-GTPγS binding, respectively.

Secondly, Ozanimod induces significant loss of S1P1 receptor cell surface expression after a 1 h treatment in the presence of 10 μM cycloheximide. Interestingly, Ozanimod demonstrates a dose-dependent effect on S1P1 receptor re-expression on the cell surface following 1 h of treatment and a 24 h washout period. Particularly, Ozanimod causes near complete and sustained loss of cell surface receptor expression at concentrations above 10 nM.

Once more, Ozanimod induces S1P1 receptor internalization and induces a reversible reduction in circulating B and CCR7+ T lymphocytes in vivo. Obviously, Oral Ozanimod reduces inflammation and disease parameters in all three autoimmune disease models.

All in all, Ozanimod is a potent and selective S1P1 and S1P5 receptor agonist.


Scott FL, et al. Br J Pharmacol. 2016 Jun;173(11):1778-92.