Pharmacological activity of a novel selective S1P1 agonist(prodrug)Syl978

Syl978 is a synthesized selective S1P1(sphingosine-1-phosphate receptor 1)agonist which is obtained based on the structural modification of fingolimod(FTY720). Biological evaluation in vitro indicated that Syl978-P, the active form of Syl978 demonstrated nanomole S1P1 agonist activity with > 500 selective over S1P3. In SD rats, oral administration of 0. 3, 1 and 3 mg/kg Syl978 significantly decrease the peripheral blood lymphocytes(PBL)in a dose-dependent manner. Oral administration of 10 mg/kg Syl978 had no effect on the heart rate of SD rats. In summary, the above results demonstrated that Syl978 exhibited great selectivity both in vitro and in vivo study, suggesting the potential therapeutic use in the treatment of autoimmune diseases.