Palosuran HCl (ACT-058362 HCl) is a specific and orally bioactive urotensin II receptor antagonist (inhibitor) with IC50 of 3.6 nM against CHO cell membranes expressing the human recombinant receptor. Palosuran HCl improves pancreatic and renal function in diabetic rats.

Physicochemical Properties

Molecular Formula	C25H31CLN4O2
Molecular Weight	454.992244958878
Exact Mass	454.213
CAS #	2469274-58-4
Related CAS #	Palosuran;540769-28-6
PubChem CID	137891318
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	6
Heavy Atom Count	32
Complexity	572
Defined Atom Stereocenter Count	0
SMILES	Cl.OC1(CC2C=CC=CC=2)CCN(CCNC(NC2C=C(C)N=C3C=CC=CC=23)=O)CC1
InChi Key	VXRLVUHHXKVQSQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H30N4O2.ClH/c1-19-17-23(21-9-5-6-10-22(21)27-19)28-24(30)26-13-16-29-14-11-25(31,12-15-29)18-20-7-3-2-4-8-20;/h2-10,17,31H,11-16,18H2,1H3,(H2,26,27,28,30);1H
Chemical Name	1-[2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl]-3-(2-methylquinolin-4-yl)urea;hydrochloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: 3.6 nM (human urotensin II receptor)[1]
ln Vitro	In TE 671 cells and recombinant CHO cells, palosuran (8 h) inhibits 125I-U-II binding to the human UT receptor with IC50s of 46.2 nM and 86 nM, respectively[1]. In CHO cells expressing human and rat UT receptors, palosuran inhibits Ca2+ mobilization in response to human U-II with IC50s of 17 and >10000 nM, respectively[1]. With an IC50 of 150 nM, palosuran (0.12-10000 nM; 20 min) inhibits the phosphorylation of MAPK induced by human U-II in recombinant CHO cells in a dose-dependent manner[1].
ln Vivo	Without lowering blood pressure, ACT-058362 (10 mg/kg/h; iv) completely reverses the decline in renal blood flow following ischemia in rats[1]. In streptozotocin-induced diabetic rats, palosuran (300 mg/kg/d; po for 16 weeks) raises insulin, improves survival, and reduces the rise in glycemia, glycosylated hemoglobin, and serum lipids[2].
Animal Protocol	Animal/Disease Models: Male Wistar rats with renal ischemia and reperfusion[1] Doses: 20 mg/kg/h for 135 min Route of Administration: Iv (continuous infusion) for 135 min Experimental Results: 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 Dramatically alter mean arterial blood pressure ( MAP) and heart rate (HR).
References	[1]. 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. [2]. The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1115-21.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (109.89 mM) H2O: 7.14 mg/mL (15.69 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.49 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.49 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.49 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1979 mL	10.9893 mL	21.9785 mL
	5 mM	0.4396 mL	2.1979 mL	4.3957 mL
	10 mM	0.2198 mL	1.0989 mL	2.1979 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.