Selexipag

Selexipag (NS-304) is an orally available and potent agonist for the Prostacyclin (PGI₂) receptor (IP receptor). IC50 & Target:Prostacyclin receptor^[1] In Vitro: Selexipag (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. Selexipag (NS-304) inhibits the binding of [³H]Iloprost to the human and rat IP receptors in a concentration-dependent manner. The K_i 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 Selexipag (NS-304) with EC₅₀ of 177nM. Selexipag (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]. In Vivo: The C_max of MRE-269 after oral administration of NS-304 is 1.1 μg/mL in rats and 9.0 μg/mL in dogs. Selexipag (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, Selexipag (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].