Selexipag 是前列环素受体激动剂，可引起肺血管舒张，用于治疗肺动脉高压。

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

NS-304 is an orally available and long-acting IP receptor agonist prodrug, and its active form, MRE-269, is highly selective for the IP receptor. NS-304 inhibits the binding of [3H]Iloprost to the human and rat IP receptors in a concentration-dependent manner. The Ki is 260 nM for the human IP receptor and 2100 nM for the rat IP receptor. The intracellular cAMP levels in hIP-CHO cells are increased in a concentration-dependent manner by treatment with NS-304 with EC50 of 177 nM. NS-304 also inhibits platelet aggregation in humans and monkeys with IC50 values of 5.5 and 3.4 μM, respectively, but it shows no inhibition in dogs (IC50 of >100 μM)[1].

The Cmax of MRE-269 after oral administration of NS-304 is 1.1 μg/mL in rats and 9.0 μg/mL in dogs. NS-304 at 1 or 3 mg/kg increases FSBF in anesthetized rats for more than 4 h after intraduodenal administration in a dose-dependent manner. In particular, NS-304 at 3 mg/kg causes a sustained increase in FSBF and exhibits a maximal increase of 93% in FSBF 1 h after administration[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].

475086-01-2

C26H32N4O4S

496.63

ACT-293987;赛乐西帕;NS-304;Uptravi

DMSO:49.7 mg/mL(100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years