ASP4058 hydrochloride is a potent, next-generation S1P receptor agonist selective for S1P1 and S1P5 with EC50 of 7.4 nM and 7.5 nM respectively. ASP4058 stimulates S1P1 and S1P5, and more than 100-times higher concentration than S1P2, S1P3, and S1P4. ASP4058 activates rS1P1 and rS1P3 comparable to cognate human S1P1 and S1P5 receptors. ASP4058 reduced the peripheral lymphocyte counts of Lewis rats as a function of dose (ED50 = 0.10 mg/kg 24 h after treatment, oral). ASP4058 (0.03, 0.1 or 0.3 mg/kg, oral, vehicle: 0.5% methylcellulose) exhibits prophylactic effect on acute monophasic EAE in rats.
