Background:

Palosuran is a potent and specific antagonist of human urotensin-II receptor with IC50 value of 3.6nM [1].

Palosuran is a nonpeptidic, potent and selective antagonist of the urotensin-II receptor. It is selective toward human receptor. The IC50 value of it to rat receptor is 1475nM. The efficacy of palosuran to inhibit Ca2+ mobilization in CHO cells also improved that palosuran is more effective to human UT receptors than to rat UT receptors with IC50 values of 17nM and more than 10μM, respectively. Besides that, palosuran inhibits the phosphorylation of MAPK with IC50 value of 150nM in recombinant CHO cells. Palosuran is selective. It shows no inhibition of other receptors involved in vascular tone regulation such as α-1 adrenoceptor, 5-hydroxytryptamine 2A receptor and endothelin receptor A. Palosuran is used as a pharmacological tool to study the role of endogenous U-II [1, 2].

参考文献:
[1] Carotenuto A, Grieco P, Rovero P, et al. Urotensin-II receptor antagonists. Current medicinal chemistry, 2006, 13(3): 267-275.
[2] Clozel M, Binkert C, Birker-Robaczewska M, et al. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin system. Journal of Pharmacology and Experimental Therapeutics, 2004, 311(1): 204-212.