AMG 369

AMG 369 is an orally active and potent dual S1P₁/S1P₅ agonist with limited activity at S1P₃ and no activity at S1P₂/S1P₄. AMG 369 reduces blood lymphocyte counts. AMG 369 delays onset and reduces severity of experimental autoimmune encephalomyelitis in rat^[1]. In Vitro:AMG 369 potently induces internalization of hS1P₁-GFP fusion protein in U2OS cells with an EC₅₀ of 0.002 μM and 98% efficacy^[1].
AMG 369 weakly induces Ca²⁺ mobilization via hS1P₃ in transfected CHO-K1 cells with an EC₅₀ of 0.888 μM and 26% efficacy^[1]. In Vivo:AMG 369 (0.01-0.1 mg/kg; p.o.; single dose) produces dose-dependent, statistically significant reductions in blood lymphocyte counts at 0.03 mg/kg (45% reduction) and 0.1 mg/kg (65% reduction) 24 hours postdose in female Lewis rats ^[1].
AMG 369 (0.1 mg/kg; p.o.; single dose) delays the onset and reduces clinical disease severity in a female Lewis rat experimental autoimmune encephalomyelitis model^[1].