Etrasimod (APD334) is a specific and orally available antagonist of the sphingosine-1-phosphate-1 (S1P1) receptor (IC50: 1.88 nM in CHO cells).

S1P1:1.88 nM (CHO cells)

在表达HA标记的S1P1的CHO细胞中，APD334的IC50值为1.88 nM。在人类S1P4和S1P5上观察到中等程度的激动作用，但与S1P1相比，无论是在效力还是效能方面均有所减少。APD334在人类S1P2和S1P3上没有表现出任何激动或拮抗作用。

APD334在所有物种中具有相对低的系统清除率（<4%的肝脏血流量）和高Cmax。在狗和猴子中，与啮齿动物相比观察到分布体积（Vss）的显著减少。口服生物利用度在40-100%范围内，末端半衰期在猴子中为6小时，而在狗中可长达29小时。

APD334 induced effects on blood lymphopenia are determined in male Sprague-Dawley rats. Briefly, male rats are given a 0 (vehicle only), 0.03 (mice only), 0.1, 0.3 or 1 mg/kg oral dose of APD334 formulated in 0.5% methylcellulose (MC) in water. Rat blood samples are collected at 0, 1, 3, 5, 8, 16, 24, 32, 48 and 72 hours post-dose. APD334 induced effects on blood lymphopenia are determined in male BALB/c mice. Briefly, male mice are given a 0 (vehicle only), 0.03 (mice only), 0.1, 0.3 or 1 mg/kg oral dose of APD334 formulated in 0.5% methylcellulose (MC) in water. Mouse blood samples are taken at 0, 1, 3, 5, 8, 16, 24 and 32 hours post-dose.