| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
human urotensin II receptor ( IC50 = 3.6 nM )
Palosuran selectively targets the urotensin II receptor (UT receptor), a G protein-coupled receptor that is activated by the endogenous peptide urotensin II. It inhibits ¹²⁵I-U-II binding to human UT receptors in membrane preparations from CHO cells with an IC₅₀ of 3.6 nM. As a non-peptidic antagonist, palosuran blocks urotensin II-mediated signaling without activating the receptor itself. |
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| 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]. In vitro, palosuran potently inhibits the urotensin II receptor with an IC₅₀ of 3.6 nM in CHO cell membranes expressing human recombinant receptors. It acts as an antagonist at the urotensin 2 receptor in both rat urotensin 2 receptor-expressing CHOK1 cells and human RMS13 cells, inhibiting urotensin 2-induced intracellular calcium mobilization. The compound's selectivity for the UT receptor has been characterized in receptor binding and functional assays. |
| 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]. In vivo, palosuran (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/day; p.o.) improves pancreatic and renal function in diabetic rats. These findings demonstrate that palosuran can modulate the urotensin II system in vivo and suggest potential therapeutic applications in renal and pancreatic diseases. |
| Enzyme Assay |
Non-cellular receptor binding assays for palosuran involve competitive radioligand binding displacement studies using membrane preparations from CHO cells expressing the human urotensin II receptor. Membranes are incubated with ¹²⁵I-urotensin II and varying concentrations of palosuran. Following incubation and filtration, bound radioactivity is measured. IC₅₀ values are determined from displacement curves.
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| Cell Assay |
In vitro cellular assays for palosuran involve treating cells expressing the urotensin II receptor with the compound and measuring receptor-mediated signaling. Functional assays typically measure intracellular calcium mobilization (as UT receptors are coupled to Gq proteins). Cells are loaded with a calcium-sensitive dye (e.g., Fluo-4) and stimulated with urotensin II in the presence of varying concentrations of palosuran. The inhibition of the calcium response is quantified to determine the IC₅₀ for antagonism.
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| Animal Protocol |
Male Wistar rats with renal ischemia and reperfusion
20 mg/kg/h for 135 min I.v. (continuous infusion) for 135 min In vivo animal experiments with palosuran are conducted in rat models of renal ischemia and diabetes. In the renal ischemia model, rats are treated with palosuran (10 mg/kg/h; i.v.), and renal blood flow is measured. In diabetic rat models, palosuran (300 mg/kg/day; p.o.) is administered, and pancreatic and renal function are assessed by measuring blood glucose, insulin levels, and markers of renal function. |
| ADME/Pharmacokinetics |
Palosuran has a molecular weight of 418.53 and a molecular formula of C₂₅H₃₀N₄O₂. It is a solid powder with a purity of ≥95%. The compound is typically stored at -20°C, protected from light and moisture. It is soluble in DMSO and other organic solvents. The compound is stable under recommended storage conditions.
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| Toxicity/Toxicokinetics |
Palosuran is a research compound for laboratory use only and is not approved for human therapeutic use. In preclinical studies, it has been generally well-tolerated at therapeutic doses. Standard laboratory safety precautions should be followed when handling the compound. It may cause skin, eye, and respiratory irritation. Appropriate personal protective equipment should be used.
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| References |
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| Additional Infomation |
Palosuran (ACT-058362; CAS 540769-28-6) is a potent, selective, and orally active urotensin II receptor antagonist with an IC₅₀ of 3.6 nM for human UT receptors. It prevents the decrease in renal blood flow after ischemia and improves pancreatic and renal function in diabetic rats. Palosuran is available from various commercial suppliers for research applications.
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| Molecular Formula |
C25H30N4O2
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|---|---|
| Molecular Weight |
418.5313
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| Exact Mass |
418.237
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| Elemental Analysis |
C, 71.74; H, 7.23; N, 13.39; O, 7.65
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| CAS # |
540769-28-6
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| Related CAS # |
Palosuran hydrochloride; 2469274-58-4
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| PubChem CID |
10173280
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| Appearance |
White to pink solid powder
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| LogP |
3.298
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
572
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(CC1)(CC2=CC=CC=C2)CCN1CCNC(NC3=CC(C)=NC4=CC=CC=C34)=O
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| InChi Key |
WYJCYXOCHXWTHG-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
1-[2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl]-3-(2-methylquinolin-4-yl)urea
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| Synonyms |
ACT058362; ACT-058362; ACT 058362; Palosuran
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: ~50 mg/mL (~119.5 mM)
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| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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