Ceralifimod is an agonist of the sphingosine-1-phosphate (S1P) receptors S1P1 and S1P5 (Kis = 0.626 and 0.574 nM, respectively). It is selective for S1P1 and S1P5 over S1P2-4 (Kis = >5,450, >5,630, and 28.8 nM, respectively). Ceralifimod induces calcium influx in CHO-K1 cells overexpressing S1P1 (EC50 = 1 nM) and cAMP accumulation in CHO-K1 cells overexpressing S1P1 or S1P5 (EC50s = 0.027 and 0.33 nM, respectively). In vivo, ceralifimod (0.03 and 0.1 mg/kg) reduces paw edema in a rat model of collagen induced arthritis (CIA). It also delays disease onset and inhibits lymphocyte infiltration of the spinal cord in a rat model of experimental autoimmune encephalomyelitis (EAE) and prevents disease relapse in a non-obese diabetic mouse model of relapsing-remitting EAE.
