Palosuran hydrochloride (C09-1165-333)

Palosuran hydrochloride (ACT-058362 hydrochloride) is a potent, selective, and orally active antagonist of urotensin II receptor , with an IC 50 of 3.6 nM for CHO cell membranes expressing human recombinant receptors. Palosuran hydrochloride can improves pancreatic and renal function in diabetic ratsIn VitroPalosuran (8 h) inhibits 125 I-U-II binding to human UT receptor, with IC 50 s of 46.2 nM on TE 671 cells and 86 nM on recombinant CHO cells. Palosuran inhibits Ca 2+ mobilization in response to human U-II in CHO cells expressing human and rat UT receptor with IC 50 s 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 IC 50 of 150 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoACT-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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male Wistar rats with renal ischemia and reperfusion Dosage: 20 mg/kg/h for 135 min Administration: I.v. (continuous infusion) for 135 min Result: Restored renal blood flow to baseline values at 30 min after reperfusion and by 60 min increased renal blood flow by 12% above baseline values. Did not significantly alter mean arterial blood pressure (MAP) and heart rate (HR).IC50& Target:IC50: 3.6 nM (human urotensin II receptor). Specifications and Purity: 10mM in DMSO. Molecular Formula: C25H31ClN4O2. Molecular Weight: 454.99.