Selexipag (ACT-293987)(NS-304) is prostacyclin receptor agonist that causes vasodilation in pulmonary vasculature and is used in the therapy of pulmonary arterial hypertension (PAH).

Selexipag是一种可口服且长效的IP受体激动剂前体化合物，其活性形式MRE-269对IP受体具有高选择性。Selexipag能够浓度依赖性地抑制[3H]伊洛前列素与人类及大鼠IP受体的结合，其对人类IP受体的Ki值为260nM，对大鼠IP受体的Ki值为2100nM。Selexipag通过处理也能够浓度依赖性地增加hIP-CHO细胞中的细胞内cAMP水平，其EC50为177nM。此外，Selexipag还能够抑制人类和猴子的血小板聚集，IC50值分别为5.5μM和3.4μM，但在狗（IC50 >100μM）中无抑制作用[1]。

MRE-269 在经口给予 Selexipag 后，其在大鼠和犬中的最大血浆浓度（Cmax）分别为 1.1 μg/mL 和 9.0 μg/mL。Selexipag 以 1 或 3 mg/kg 的剂量，通过十二指肠给药后，能在麻醉大鼠中以剂量依赖性的方式增加前列腺素合成酶活性（FSBF），持续时间超过 4 小时。特别地，3 mg/kg 的 Selexipag 能持续增加 FSBF，并在给药后 1 小时显示出最大增加率为 93%[1]。

NS-304 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1]. CHO cells expressing the human IP receptor (hIP-CHO cells) are seeded at 1×105 cells/well in a 24-well plate and cultured for 48 h. The cells are washed with Dulbecco's phosphate-buffered saline without divalent cations, preincubated in the medium for 1 h at 37°C, and then incubated for 15 min at 37°C with medium containing each drug in the presence of 500 μM 3-isobutyl-1-methylxanthine. The medium is removed, and perchloric acid solution is added to terminate the reaction. Intracellular cAMP levels are measured by enzymelinked immunosorbent assay[1].