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

Physicochemical Properties

Molecular Formula	C25H30N4O2
Molecular Weight	418.5313
Exact Mass	418.237
Elemental Analysis	C, 71.74; H, 7.23; N, 13.39; O, 7.65
CAS #	540769-28-6
Related CAS #	Palosuran hydrochloride; 2469274-58-4
PubChem CID	10173280
Appearance	White to pink solid powder
LogP	3.298
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	6
Heavy Atom Count	31
Complexity	572
Defined Atom Stereocenter Count	0
SMILES	OC(CC1)(CC2=CC=CC=C2)CCN1CCNC(NC3=CC(C)=NC4=CC=CC=C34)=O
InChi Key	WYJCYXOCHXWTHG-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H30N4O2/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)
Chemical Name	1-[2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl]-3-(2-methylquinolin-4-yl)urea
Synonyms	ACT058362; ACT-058362; ACT 058362; Palosuran
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
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	human urotensin II receptor ( IC50 = 3.6 nM )
ln Vitro	Palosuran (8 h)inhibits 125I-U-II binding to the 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 receptors with IC50s of 17 and >10000 nM, respectively[1]. Palosuran (0.12-10000 nM; 20 min) has an IC50 of 150 nM and inhibits human U-II induced MAPK phosphorylation in a dose-dependent manner in recombinant CHO cells[1].
ln Vivo	ACT-058362 (10 mg/kg/h; i.v.)completely stops the reduction in renal blood flow while keeping blood pressure stable in rats experiencing ischemia[1]. Palosuran (300 mg/kg/d; p.o. for 16 weeks) slows the rise in serum lipids, glycosylated hemoglobin, and glycemia in streptozotocin-induced diabetic rats while also increasing insulin production and improving survival[2].
Animal Protocol	Male Wistar rats with renal ischemia and reperfusion 20 mg/kg/h for 135 min I.v. (continuous infusion) for 135 min
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 S. [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 (~119.5 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (3.99 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 16.7 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: 1.67 mg/mL (3.99 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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: ≥ 1.67 mg/mL (3.99 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 16.7 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	2.3893 mL	11.9466 mL	23.8931 mL
	5 mM	0.4779 mL	2.3893 mL	4.7786 mL
	10 mM	0.2389 mL	1.1947 mL	2.3893 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.