NS-304

• CAT Number: I003651
• CAS Number: 475086-01-2
• Molecular Formula: C26H32N4O4S
• Molecular Weight: 496.6
• Purity: ≥95%
• Synonyms: 2-(4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)-N-(methylsulfonyl)acetamide
• Target: Prostanoid Receptors
• InChIKey: QXWZQTURMXZVHJ-UHFFFAOYSA-N

NS-304(Selexipag; ACT-293987) is an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension.IC50 value:Target:NS-304 is an orally available and potent agonist for the PGI(2) receptor (IP receptor). The inhibition constant (K(i)) of MRE-269 for the human IP receptor was 20 nM; in contrast, the K(i) values for other prostanoid receptors were >2.6 microM. MRE-269 was therefore a highly selective agonist for the IP receptor. The plasma concentrations of MRE-269 remained near peak levels for more than 8 h after oral administration of NS-304 to rats and dogs, and NS-304 increased femoral skin blood flow in rats in a long-lasting manner without affecting the hemodynamics. These findings indicate that NS-304 acts as a long-acting IP receptor agonist in vivo. The continuous vasodilation evoked by NS-304 was not attenuated by repeated treatment, indicating that NS-304 is unlikely to cause severe desensitization of the IP receptor in rats.

Reference

1:A comparison of vasodilation mode among selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide]), its active metabolite MRE-269 and various prostacyclin receptor agonists in rat, porcine and human pulmonary arteries. Fuchikami C, Murakami K, Tajima K, Homan J, Kosugi K, Kuramoto K, Oka M, Kuwano K.Eur J Pharmacol. 2017 Jan 15;795:75-83. doi: 10.1016/j.ejphar.2016.11.057. Epub 2016 Dec 3. PMID: 27919660 2: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. Kuwano K, Hashino A, Noda K, Kosugi K, Kuwabara K.J Pharmacol Exp Ther. 2008 Sep;326(3):691-9. doi: 10.1124/jpet.108.138305. Epub 2008 Jun 13. PMID: 18552131 Free Article3:2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. Kuwano K, Hashino A, Asaki T, Hamamoto T, Yamada T, Okubo K, Kuwabara K.J Pharmacol Exp Ther. 2007 Sep;322(3):1181-8. Epub 2007 Jun 1. PMID: 17545310 Free Article