Ceralifimod (ONO-4641) is a potent agonist for sphingosine 1-phosphate receptors 1 and 5 (EC50s: 27.3, 334 pM for human S1P receptor 1 and 5).

S1P5 (human):334 pM（EC50）, S1P1 (human):（EC50）27.3 pM

Ceralifimod induces S1P1 down-regulation in a concentration-dependent manner and by approximately 90% at a concentration of 25 nM. Ceralifimod has an agonistic action for S1P1 and S1P5. However, there is no difference between humans and rats in the agonistic action of Ceralifimod for S1P1.

The maximum clinical scores decrease dose-dependently in the Ceralifimod groups and those in the Ceralifimod 0.03 and 0.1 mg/kg groups are significantly lower than that in the control group. In the Ceralifimod 0.1 mg/kg group, paralysis is inhibited completely in seven of eight animals. In contrast, none of the animals in the Ceralifimod 0.1 mg/kg group have a relapse; that is, Ceralifimod completely prevents relapse at a dose of 0.1 mg/kg. In normal NOD mice, the number of peripheral blood lymphocytes is decreased by approximately 20, 60, and 80% at 24 h after a single oral dose of 0.01, 0.03, and 0.1 mg/kg of Ceralifimod, respectively. In the control group of the NOD mouse model of relapsing-remitting EAE, the relapse rate is 90.0%, and two of the nine animals die. In the Ceralifimod groups, two of the nine animals in the 0.01 mg/kg died.