Validating a Selective S1P1 Receptor Modulator Sy1930 for Psoriasis Treatment

Psoriasis is a chronic inflammatory skin disease characterized by red, scaly and raised plaques. Thus far, T-cell infiltration is one of the most prominent pathogenic triggers, however, the exact molecular mechanisms underlying psoriasis have not been clearly established. Sphingolipid sphingosine-1-phosphate (SW) is a lysophospholipid regulator modulating a variety of immune cell trafficking via interactions with its cognate receptors, S1P(1-5) . Activation of S1P signaling has recently emerged as a novel therapeutic avenue for psoriasis treatment. Here, we test a newly developed selective S1P, modulator, Sy1930, in four different psoriasis animal models. Our data reveals that oral administration of Sy1930 can induce strong anti-proliferative and anti-inflammatory effects. Specifically, Sy1930 decreases the pathological thickening of back skin induced by sodium lauryl sulfate (SLS), inhibits the proliferation of basal cells in a vaginal epithelium model and increases the granular layer scales in a mouse tail assay. Moreover, Sy1930 can ameliorate the parakeratosis and acanthosis as well as improve granular layer composition and decrease the thickening of epidermis in a propranolol-induced guinea pig psoriasis model. Therefore, we demonstrate that Sy1930 is a promising candidate for psoriasis therapy in clinical.