Ponesimod

Ponesimod (ACT-128800) is a potent, selective and orally active agonist of S1P₁, with an IC₅₀ of 6 nM in a radioligand binding assay. Ponesimod activates S1P₁-mediated signal transduction with high potency (EC₅₀=5.7 nM). Ponesimod can protect against lymphocyte-mediated tissue inflammation^[1][2][3]. In Vitro:Ponesimod activates human S1P_1-5 receptors with EC₅₀s of 5.7, >10000, 105, 1108 and 59.1 nM respectively in GTPγS binding assay^[2].
Ponesimod activates S1P₁ receptors with EC₅₀s of 5.7, 1.9, and 1.4 nM for human, rat, and mouse S1P receptors respectively^[2]. In Vivo:Ponesimod (30 and 175 mg/kg; once daily p.o. for 8 d) prevents delayed-type hypersensitivity in mice^[2].
Ponesimod (30 mg/kg by gavage 3 h before and 6 h after adjuvant injection followed by 100 mg/kg/day by administration as food admix for 18 days) prevents adjuvant-induced arthritis in rats^[2].
Ponesimod (0.3-100 mg/kg; a single oral gavage) causes a dose-dependent reduction in lymphocyte count, with a plateau effect being reached at 3 mg/kg in rats^[2].
Ponesimod (100 mg/kg; once daily oral gavage for 7 d) results in a lymphocyte count reduction to 1900 lymphocytes/μL, and this effect is maintained over the entire 7 days studies. Lymphocyte count returned to baseline levels within 48 h after discontinuation of dosing^[2].