NS 304

NS 304 is an IP receptor agonist and a prodrug form of MRE-269 (Item No. 10010412).¹ It binds to the IP receptor (K_i = 260 nM for the human receptor) and induces cAMP accumulation in CHO cells expressing the human IP receptor (EC₅₀ = 177 nM). NS 304 is selective for the IP receptor over DP, EP_1-4, FP, and TP receptors (K_is = >10 µM for all). NS 304 inhibits the aggregation of isolated human and monkey but not dog platelet-rich plasma (IC₅₀s = 5.5, 3.4, and >100 µM, respectively). It increases femoral skin blood flow in rats when administered at 1 or 3 mg/kg intraduodenally. NS 304 (1 mg/kg) increases survival and decreases right ventricular systolic pressure and hypertrophy in a rat model of pulmonary arterial hypertension induced by monocrotaline (Item No. 16666).² Formulations containing NS 304 have been used in the treatment of pulmonary arterial hypertension.

WARNING This product is not for human or veterinary use.

1. Kuwano, K., Hashino, A., Asaki, T., et al. 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J. Pharmacol. Exp. Ther. 322(3), 1181-1188 (2007).

2. Kuwano, K., Hashino, A., Noda, K., et al. A long-acting and highly selective prostacyclin receptor agonist prodrug, 2-{4-[5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide (NS-304), ameliorates rat pulmonary hypertension with unique relaxant responses of its active form, {4-[5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (MRE-269), on rat pulmonary artery. J. Pharmacol. Exp. Ther. 326(3), 691-699 (2008).