| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
IC50: 3.6 nM (human urotensin II receptor)[1]
Urotensin-II receptor (UT). Palosuran is a specific and competitive antagonist of the UT receptor, which is the target for the potent vasoconstrictor peptide urotensin-II (U-II). It blocks the binding of U-II to its receptor, thereby inhibiting its downstream effects. |
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| 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].
In a cell-based assay using CHO-K1 cells expressing the human UT receptor, palosuran inhibits U-II-induced calcium mobilization with an IC50 of 3.6 nM. This demonstrates its potent functional antagonist activity. It also shows over 100-fold selectivity for the human UT receptor over other GPCRs and ion channels. |
| 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].
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| Enzyme Assay |
A cell-free radioligand binding assay is performed using membrane preparations from CHO-K1 cells expressing the human UT receptor. Membranes are incubated with [125I]-urotensin-II and varying concentrations of palosuran hydrochloride. After filtration to separate bound from free ligand, the radioactivity is counted to determine the compound's Ki.
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| Cell Assay |
CHO-K1 cells stably expressing the human UT receptor are seeded in 96-well plates and loaded with a calcium-sensitive fluorescent dye. Cells are pre-incubated with palosuran hydrochloride and then stimulated with urotensin-II. The reduction in fluorescence signal (indicative of calcium flux) is measured to calculate the IC50 of the antagonist (3.6 nM).
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| 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). In vivo efficacy can be evaluated in several rodent models. For example, in a rat model of ischaemia-induced acute renal failure, palosuran is administered orally. Renal blood flow is measured by laser Doppler flowmetry. Other endpoints include plasma creatinine levels, histological scoring of kidney damage, and urinary protein excretion. |
| ADME/Pharmacokinetics |
Palosuran is an orally active antagonist, indicating it is absorbed from the gastrointestinal tract. In Sprague-Dawley rats, the oral bioavailability was reported to be 40-50%. The plasma half-life (t1/2) in humans was approximately 4-6 hours in early clinical studies, supporting multiple daily dosing.
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| Toxicity/Toxicokinetics |
In early-phase clinical trials, palosuran was generally well-tolerated in healthy volunteers. The most common side effects were mild to moderate headaches and gastrointestinal issues. No serious adverse events were reported. However, its development was limited due to lack of clear efficacy in some clinical endpoints.
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| References |
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| Additional Infomation |
Palosuran was a promising drug candidate that reached Phase II clinical trials for the treatment of diabetic nephropathy. The compound was developed to treat kidney diseases by improving renal blood flow, as urotensin-II is a potent renal vasoconstrictor. While initial Phase II studies showed some positive effects on renal function, the results were not conclusive enough to support further development for this indication.
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| Molecular Formula |
C25H31CLN4O2
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|---|---|
| Molecular Weight |
454.992244958878
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| Exact Mass |
454.213
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| CAS # |
2469274-58-4
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| Related CAS # |
Palosuran;540769-28-6
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| PubChem CID |
137891318
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
572
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.OC1(CC2C=CC=CC=2)CCN(CCNC(NC2C=C(C)N=C3C=CC=CC=23)=O)CC1
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| InChi Key |
VXRLVUHHXKVQSQ-UHFFFAOYSA-N
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| 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
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| Chemical Name |
1-[2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl]-3-(2-methylquinolin-4-yl)urea;hydrochloride
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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 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)
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| Solubility (In Vitro) |
DMSO: 50 mg/mL (109.89 mM)
H2O: 7.14 mg/mL (15.69 mM) |
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| 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. View More
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. |
| 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.
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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