820240-77-5

AUY954 is an orally bioavailable and selective agonist of the sphingosine-1-phosphate receptor 1 (S1P₁; EC₅₀ = 1.2 nM for stimulating GTPγS binding to S1P₁ in CHO cells). It is highly selective for the S1P₁ receptor with EC₅₀ values of >10,000, 1,210, >1,000, and 340 nM for S1P₂, S1P₃, S1P₄, and S1P₅ receptors, respectively. AUY954 reduces circulating lymphocytes and prevents rejection of rat heart allografts. In a rat model of experimental autoimmune neuritis, chronic treatment with AUY954 (10 mg/kg), starting on the day of immunization, almost completely prevents peripheral paralysis. In the same model, it also decreases T cell, B cell, and macrophage infiltration and perivascular demyelination in sciatic nerves.