CAY10441

CAY10441 is an antagonist of the IP receptor.¹ It is selective for the IP receptor over the prostaglandin E₂ (PGE₂) receptor subtypes EP₁, EP₂, EP₃, and EP₄, the FP and TP receptors, and a panel of 30 other receptors and ion channels but does bind to the α_2A-adrenergic and imidazoline I₂ receptors. CAY10441 inhibits carbaprostacyclin-induced cAMP accumulation in SH-SY5Y cells (pK_B = 8.8) and vasorelaxation of isolated human pulmonary arteries induced by the IP receptor agonist cicaprost (pA₂ = 8.2).^1,2 It also decreases cicaprost-induced inhibition of platelet aggregation in human platelet-rich plasma.² CAY10441 reduces acetic acid-induced writhing and carrageenan-induced paw hyperalgesia in rats (ED₅₀s = 4 and 2.8 mg/kg, respectively).¹

WARNING This product is not for human or veterinary use.

1. Clark, R.D., Jahangir, A., Severance, D., et al. Discovery and SAR development of 2-(phenylamino) imidazolines as prostacyclin receptor antagonists. Bioorg. Med. Chem. Lett. 14(4), 1053-1056 (2004).

2. Jones, R.L., Wise, H., Clark, R., et al. Investigation of the prostacyclin (IP) receptor antagonist RO1138452 on isolated blood vessel and platelet preparations. Br. J. Pharmacol. 149(1), 110-120 (2006).

Matsumoto, N., Singh, N., Lee, K.S., et al. The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms. Prostaglandins Other Lipid Mediat. 162, 106662 (2022).

Fuchikami, C., Murakami, K., Tajima, K., et al. 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. Eur. J. Pharmacol. 795, 75-83 (2017).

Iyú, D., Jüttner, M., Glenn, J.R., et al. PGE₁ and PGE₂ modify platelet function through different prostanoid receptors. Prostaglandins Other Lipid Mediat. 94(1-2), 9-16 (2011).