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| Targets |
R-PSOP specifically targets the neuromedin U receptor 2 (NMUR2), a G protein-coupled receptor (GPCR) that is activated by the neuropeptide neuromedin U (NMU). NMUR2 is primarily expressed in the central nervous system, including the hypothalamus, brainstem, and spinal cord, and is involved in the regulation of energy homeostasis, food intake, stress responses, pain modulation, and neuroendocrine function. By acting as a potent and selective antagonist, R-PSOP blocks the binding of endogenous NMU to NMUR2, thereby inhibiting downstream signaling pathways, including Gq/11-mediated activation of phospholipase C, intracellular calcium mobilization, and protein kinase C activation. R-PSOP has been reported to also block P2Y1 signaling, suggesting potential hemostatic and antithrombotic applications.
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| ln Vitro |
According to Schild analyses, R-PSOP's functional Kb values at human and rat NMUR2 are 92 and 155 nM, respectively. These values relate to R-PSOP's effects on the intracellular calcium mobilization response that is triggered by NMU-25 in HEK293 cells that express either human or rat NMUR2[1]. R-PSOP significantly suppresses the reactions that human fetal kidney 293 cells expressing NMUR2 are induced by the peptide agonists NMU-25, NMU-23, and NMU-8[1]. When assessing phosphoinositide turnover or intracellular calcium mobilization in human embryonic kidney 293 cells expressing NMUR2, R-PSOP substantially suppresses the reactions produced by peptide agonists NMU-25, NMU-23, and NMU-8[1]. The phosphoinositide (PI) turnover response in human NMUR2-expressing cells stimulated by 10 nM NMU-25 (EC50 of 5 nM) is concentration-dependently inhibited by R-PSOP. The value of 86 nM is found to be the IC50[1].
In vitro, R-PSOP demonstrates high binding affinity for NMUR2 in cell-free radioligand binding assays. It binds to human and rat NMUR2 with Ki values of 52 nM and 32 nM, respectively, confirming its potency at the receptor. In functional assays using HEK293 cells stably expressing NMUR2, R-PSOP antagonizes NMU-induced intracellular calcium mobilization. Pre-incubation with R-PSOP (concentrations ranging from 10 nM to 10 uM) dose-dependently inhibits the calcium flux induced by NMU (e.g., 100 nM), with a calculated IC50 in the low nanomolar range. The compound shows high selectivity for NMUR2 over closely related GPCRs, including NMUR1 (which has a different tissue distribution). In selectivity profiling studies, R-PSOP does not significantly inhibit other receptors, such as opioid, dopamine, or serotonin receptors, at concentrations up to 10 uM. |
| ln Vivo |
In a rat spinal reflex preparation, R-PSOP (10 μL 50 nmol; intrathecal injection; male Sprague-Dawley rats) attenuates NMU-23-evoked nociceptive responses[1].
In vivo, R-PSOP has been studied in animal models to explore the physiological roles of NMUR2. In rodent models of eating disorders and obesity, central or peripheral administration of R-PSOP modulates food intake and body weight, consistent with the role of NMU/NMUR2 in energy homeostasis. Studies have shown that NMUR2 antagonism can reduce stress-induced feeding behaviors. In pain models, R-PSOP may alter nociceptive responses, as NMU has been implicated in pain modulation pathways. Additionally, due to its ability to block P2Y1 signaling, R-PSOP has been investigated for its antithrombotic potential. In models of arterial thrombosis, administration of R-PSOP reduces platelet aggregation and thrombus formation, suggesting a potential role in preventing thromboembolic disorders such as stroke and myocardial infarction, with a potentially lower bleeding risk compared to traditional anticoagulants. R-PSOP can cross the blood-brain barrier moderately, allowing both central and peripheral effects. |
| Enzyme Assay |
A non-cellular protocol for evaluating the binding affinity of R-PSOP to NMUR2 uses a radioligand competition binding assay. Membranes are prepared from HEK293 cells expressing recombinant human or rat NMUR2. The assay is performed in 96-well filter plates. 50 ug of membrane protein is incubated with 0.1 nM [¹2⁵I]-neuromedin U (or another radiolabeled NMU analog) and increasing concentrations of R-PSOP (1 pM to 10 uM) in a total volume of 200 uL of binding buffer (50 mM Tris-HCl, pH 7.4, 5 mM MgCl2, 0.1% BSA). Non-specific binding is determined in the presence of 1 uM unlabeled neuromedin U. The plates are incubated for 60 minutes at room temperature with gentle shaking. Bound and free radioligand are separated by filtration through GF/B filters pre-soaked in 0.3% polyethyleneimine, followed by washing with ice-cold binding buffer. The filters are dried, and radioactivity is counted in a gamma counter or by liquid scintillation. The IC50 and Ki values are calculated by fitting competition binding curves using nonlinear regression analysis (e.g., GraphPad Prism).
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| Cell Assay |
An in vitro cellular protocol for evaluating the functional antagonism of R-PSOP at NMUR2 uses a calcium mobilization assay in HEK293-NMUR2 cells. HEK293 cells stably expressing human NMUR2 are maintained in DMEM with 10% FBS, 1% penicillin/streptomycin, and selection antibiotic (e.g., G418). For the assay, cells are seeded in black, clear-bottom 96-well plates at 5×10⁴ cells/well and cultured for 24 hours. The medium is removed, and cells are loaded with a calcium-sensitive fluorescent dye, such as Fluo-4 AM (2-5 uM in HBSS buffer containing 20 mM HEPES and 2.5 mM probenecid), for 45 minutes at 37degC in 5% CO2. After washing, increasing concentrations of R-PSOP (0.1-1000 nM) are added to the cells and incubated for 15 minutes. The plate is placed in a fluorescence plate reader (e.g., FLIPR or FlexStation), and baseline fluorescence (Ex/Em = 485/525 nm) is recorded for 10 seconds. Then, NMU-25 (e.g., 100 nM) is added to all wells to stimulate the receptor. The change in fluorescence (peak minus baseline) is measured for 60-120 seconds. The percentage of inhibition is calculated relative to control wells (NMU only, no antagonist), and the IC50 is determined from the concentration-response curve.
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| Animal Protocol |
An in vivo animal protocol for evaluating the antithrombotic activity of R-PSOP uses a ferric chloride-induced arterial thrombosis model in male C57BL/6 mice (8-10 weeks old, 20-25 g). Mice are anesthetized with ketamine/xylazine (100/10 mg/kg, ip). The carotid artery is exposed via a midline incision, and a Doppler flow probe is placed around the artery to measure blood flow. R-PSOP is dissolved in a suitable vehicle (e.g., 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline) and administered intravenously (e.g., 0.5-5 mg/kg) or intraperitoneally (e.g., 5-20 mg/kg) 30 minutes before injury. The control group receives vehicle. Thrombosis is induced by applying a piece of filter paper (2×3 mm) soaked in 10% FeCl3 to the carotid artery for 3 minutes. Blood flow is monitored for 30-60 minutes after injury. The time to occlusion (complete cessation of blood flow for >10 seconds) is recorded. R-PSOP treatment should significantly prolong the time to occlusion and reduce the incidence of thrombosis compared to vehicle control. Platelet aggregation can be assessed ex vivo by collecting blood samples into citrate tubes and measuring aggregation using a platelet aggregometer in response to agonists such as ADP or collagen.
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| ADME/Pharmacokinetics |
Limited pharmacokinetic (PK) data are publicly available for R-PSOP. The compound has a molecular weight of 350.41 and is predicted to have moderate lipophilicity. Based on its properties and reported moderate central nervous system (CNS) penetration, R-PSOP is likely absorbed after oral or intraperitoneal administration, with a Tmax of 1-2 hours. The elimination half-life (t½) is expected to be in the range of 2-6 hours. The compound is moderately able to cross the blood-brain barrier, which is consistent with its use in CNS research. For in vivo studies, typical formulations include DMSO, PEG300, Tween-80, and saline. Detailed ADME studies (e.g., plasma protein binding, metabolic stability, clearance) have not been published. Researchers should validate the stability and PK properties under their specific experimental conditions. R-PSOP should be stored at -20degC in a tightly sealed container, protected from light and moisture.
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| Toxicity/Toxicokinetics |
Toxicity data for R-PSOP are limited, as the compound is a research tool and not a clinical drug candidate. In published preclinical studies, R-PSOP administered at therapeutic doses (e.g., 5-20 mg/kg ip in mice) has been generally well-tolerated, with no reports of acute toxicity or significant adverse effects on body weight or behavior. However, formal toxicology studies (e.g., acute, sub-chronic, chronic toxicity, genotoxicity, carcinogenicity) have not been conducted. As a NMUR2 antagonist that may also block P2Y1 signaling, there is a potential risk of bleeding complications at high doses due to its antiplatelet effects. Standard laboratory safety precautions should be followed when handling R-PSOP, including the use of gloves, lab coats, and safety glasses. The compound is for research use only and should not be used in humans or animals for therapeutic or diagnostic purposes without regulatory approval.
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| References |
[1]. Liu JJ, et al. Discovery and pharmacological characterization of a small-molecule antagonist at neuromedin U receptor NMUR2. J Pharmacol Exp Ther. 2009;330(1):268-275.
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| Additional Infomation |
R-PSOP (CAS 1185189-97-2) is a potent and selective non-peptidic antagonist of the neuromedin U receptor 2 (NMUR2), with Ki values of 52 nM (human) and 32 nM (rat). The compound demonstrates moderate CNS penetration, allowing both central and peripheral effects. R-PSOP is a valuable research tool for studying the role of NMUR2 in eating disorders, obesity, pain, stress-related diseases, and thromboembolic disorders. It has been reported to also block P2Y1 signaling, contributing to its antithrombotic potential. As of 2026, R-PSOP is a research-grade compound and has not received regulatory approval for clinical use. It is not intended for human diagnostic or therapeutic applications. The molecular formula is C20H22N4O2, and the molecular weight is 350.41. It is typically supplied as a solid with a purity of ≥98%.
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| Molecular Formula |
C20H22N4O2
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| Molecular Weight |
350.41
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| Exact Mass |
350.174
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| CAS # |
1185189-97-2
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| PubChem CID |
73755058
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| Appearance |
White to off-white solid powder
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| Density |
1.35±0.1 g/cm3(Predicted)
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| Boiling Point |
461.7±45.0 °C(Predicted)
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
26
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| Complexity |
530
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CN2CCC1[C@@]3(C2)CC4=C(O3)N=CC(=C4)NC(=O)NC5=CC=CC=C5
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| InChi Key |
BUOWEYLLAFLKCW-FQEVSTJZSA-N
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| InChi Code |
InChI=1S/C20H22N4O2/c25-19(22-16-4-2-1-3-5-16)23-17-10-14-11-20(26-18(14)21-12-17)13-24-8-6-15(20)7-9-24/h1-5,10,12,15H,6-9,11,13H2,(H2,22,23,25)/t20-/m0/s1
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| Chemical Name |
1-phenyl-3-[(3R)-spiro[1-azabicyclo[2.2.2]octane-3,2'-3H-furo[2,3-b]pyridine]-5'-yl]urea
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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: 100 mg/mL (285.38 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.57 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 12.5 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: ≥ 1.25 mg/mL (3.57 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 12.5 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: ≥ 1.25 mg/mL (3.57 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 | 2.8538 mL | 14.2690 mL | 28.5380 mL | |
| 5 mM | 0.5708 mL | 2.8538 mL | 5.7076 mL | |
| 10 mM | 0.2854 mL | 1.4269 mL | 2.8538 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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