Palosuran_product_DataBase

Bioactivity

Palosuran (ACT-058362) is a potent, selective, and orally active antagonist of urotensin II receptor, with an IC50 of 3.6 nM for CHO cell membranes expressing human recombinant receptors. Palosuran can improves pancreatic and renal function in diabetic rats[1][2].

Target

IC50: 3.6 nM (human urotensin II receptor)

Invitro

Palosuran (8 h) inhibits 125I-U-II binding to human UT receptor, with IC50s of 46.2 nM on TE 671 cells and 86 nM on recombinant CHO cells[1].Palosuran inhibits Ca2+ mobilization in response to human U-II in CHO cells expressing human and rat UT receptor with IC50s of 17 and >10000 nM, respectively[1].Palosuran (0.12-10000 nM; 20 min) inhibits human U-II induced MAPK phosphorylation in a dose-dependent manner in recombinant CHO cells, with an IC50 of 150 nM[1].

In Vivo

ACT-058362 (10 mg/kg/h; i.v.) fully prevents the decrease in renal blood flow after ischemia in rats without decreasing blood pressure[1].Palosuran (300 mg/kg/d; p.o. for 16 weeks) improves the survival, increases insulin, and slows the increase in glycemia, glycosylated hemoglobin, and serum lipids in streptozotocin-induced diabetic rats[2]. Animal Model:

Name

Palosuran

CAS

540769-28-6

Formula

C25H30N4O2

Molar Mass

418.53

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Clozel 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 S [2]. Clozel M, et al. The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1115-21.

PeptideDB

Palosuran

CAS: 540769-28-6 F: C25H30N4O2 W: 418.53