Ponesimod (ACT-128800) is an orally available sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) agonist with potential immunomodulating activity.

S1P1 receptor:5.7 nM(EC50)

相较于S1P的活性，ponesimod在人类重组受体上的活性对于S1P1高出4.4倍，而对于人类S1P3的活性则低150倍。因此，相对于天然配体[1]，ponesimod对人类S1P1的选择性大约是对S1P3的650倍。

Ponesimod是一种新型、高效且选择性的S1P1受体激动剂，具备使外周血淋巴细胞计数在停药后迅速恢复的药代动力学特性。Ponesimod能够阻止延迟型超敏反应小鼠皮肤中的水肿形成、炎症细胞积聚和细胞因子释放，并且还可防止佐剂诱导关节炎大鼠爪体积增加和关节炎症。通过选择性激活S1P1，Ponesimod不仅可减少血液中淋巴细胞计数，还能预防淋巴细胞介导的组织炎症模型中的炎症。因此，在动物的自身免疫模型及人体自身免疫病中，通过其对T细胞和B细胞血液计数的影响，Ponesimod有可能展现出有效性，使之成为治疗自身免疫疾病的新疗法选择[1]。Ponesimod在停药1周内被清除，其药理作用可迅速逆转[2]。

The enzymatic reactions are conducted in duplicate at room temperature for 1 hour in a 50 μL mixture containing PKMT assay buffer, substrate coated plate, 10 M SAM, a HMT enzyme (EZH2 (800 ng/reaction), MLL (300 ng/reaction), PRMT1 (0.5 ng/reaction), SUV39H1 (75 ng/reaction) and UNC0638 (0-1.25 μM). After enzymatic reactions, 100 μL of first antibody is added to each well and the plate is incubated at room temperature for an additional 1 h. 100 μL of secondary antibody is added to each well and the plate is incubated at room temperature for an additional 30 min. 100 μL of developer reagents are added to wells and luminescence is measured using a BioTek SynergyTM 2 microplate reader. Enzyme activity assays are performed in duplicates at each concentration. The luminescence data are analyzed using the computer software, Graphpad Prism[1].