Palosuran

A potent and specific antagonist of human Urotensin (UT) receptor; inhibits 125I-U-II binding to human UT receptors in membrane preparations from CHO cells carrying the human UT receptors with IC50 of 3.6 nM; prevents the development of acute renal failure and the histological consequences of ischemia in rats.Ischemia Discontinued (In Vitro) :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.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.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. (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.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.