| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
mGluR2 9 nM (IC50)
mGluR2 (metabotropic glutamate receptor 2). mGluR2 antagonist 1 is a selective negative allosteric modulator (NAM) with an IC50 of 9 nM. It demonstrates high selectivity for mGluR2 over other mGlu receptor subtypes. The compound exhibits excellent brain permeability, making it suitable for central nervous system research. |
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| ln Vitro |
In vitro, mGluR2 antagonist 1 functions as a negative allosteric modulator, binding to an allosteric site on mGluR2 and reducing receptor activation without competing with glutamate for the orthosteric binding site. At 9 nM IC50, it potently inhibits mGluR2-mediated signaling. The compound shows high selectivity for mGluR2 over other mGlu receptor subtypes in selectivity panels. In vitro efficacy is typically assessed using calcium mobilization or IP accumulation assays in cells expressing recombinant mGluR2.
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| ln Vivo |
mGluR2 antagonist 1 (Compound 25) has good efficacy at 10 mg/kg in the mouse delayed non-match to position experiment and reverses the effects of mGluR2 agonist LY379268 in amphetamine-induced hyperlocomotion in vivo.
In vivo, mGluR2 antagonist 1 (Compound 25) effectively counteracts the effects of the mGluR2 agonist LY379268 on amphetamine-induced hyperlocomotion in mice. It exhibits significant efficacy in the mouse delayed non-match to position assay at a dosage of 10 mg/kg, indicating effects on working memory. The compound's high oral bioavailability and brain permeability make it suitable for studies of mGluR2 function in CNS disorders. |
| Enzyme Assay |
Standard cell-free binding assays for mGluR2 antagonist 1 use membrane preparations from HEK-293 cells stably expressing human mGluR2. Membranes (15-25 microg protein) are incubated with 5-10 nM [3H]LY341495 (or a selective mGluR2 radioligand) and varying concentrations of the test compound (0.01-1000 nM) in 50 mM Tris-HCl buffer pH 7.4 containing 2.5 mM CaCl2 and 5 mM MgCl2 for 60 minutes at room temperature. Non-specific binding is determined in the presence of 10 microM LY341495 or 1 mM L-glutamate. Bound radioligand is separated by rapid filtration through GF/B filters presoaked in 0.5% polyethyleneimine, followed by three washes with ice-cold buffer. Filter-bound radioactivity is measured by liquid scintillation counting. For allosteric binding studies, radiolabeled positive allosteric modulators may be used to directly assess binding to the allosteric site. IC50 values (9 nM) are calculated by nonlinear regression.
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| Cell Assay |
For functional in vitro assays, HEK-293 or CHO cells stably expressing human mGluR2 are seeded in 96-well plates (40,000 cells/well) in DMEM/F-12 medium supplemented with 10% FBS and selection antibiotics for 48 hours. For calcium mobilization assays, cells are co-transfected with a promiscuous G protein (Galpha15) to couple mGluR2 to calcium signaling. Cells are loaded with Fluo-4 AM (2.5 microM) in HBSS buffer containing 20 mM HEPES and 2.5 mM probenecid for 60 minutes at 37degC. Cells are pre-incubated with varying concentrations of mGluR2 antagonist 1 (0.01-1000 nM) for 5-10 minutes, then stimulated with an EC80 concentration of a mGluR2 agonist (e.g., glutamate or DCG-IV). Fluorescence is measured using a fluorescence plate reader (excitation 485 nm, emission 525 nm). Percentage inhibition of the agonist response is calculated, and IC50 values are determined from concentration-inhibition curves. For IP accumulation assays, cells are labeled with [3H]myo-inositol, and inositol phosphates are quantified after agonist stimulation in the presence of antagonist. Positive allosteric modulation is confirmed by testing mGluR2 antagonist 1 in combination with orthosteric agonists at multiple concentrations.
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| Animal Protocol |
In vivo animal studies with mGluR2 antagonist 1 typically use male C57BL/6 mice (20-30 g) or Sprague-Dawley rats (200-300 g). The compound is formulated in 10% DMSO/40% PEG300/5% Tween-80/45% saline or 0.5% methylcellulose and administered orally (1-30 mg/kg) or intraperitoneally (0.5-10 mg/kg) 30-60 minutes before testing. For the amphetamine-induced hyperlocomotion model, mice are placed in locomotor activity chambers, and baseline activity is recorded for 30 minutes. Amphetamine (2.5 mg/kg i.p.) is administered, and locomotor activity is recorded for an additional 60-120 minutes. mGluR2 antagonist 1 is administered 15-30 minutes before amphetamine. The ability of the compound to reverse the hyperlocomotor effect of amphetamine in the presence of an mGluR2 agonist (e.g., LY379268) is assessed. For the delayed non-match to position (DNMTP) assay, rats are trained in operant chambers with two retractable levers. Each trial consists of a sample phase (one lever presented) followed by a delay period (0-30 seconds), then a choice phase (both levers presented, correct choice is the non-sample lever). Accuracy and response latency are recorded. mGluR2 antagonist 1 (10 mg/kg p.o.) is administered 30-60 minutes before testing, and effects on working memory performance are evaluated. Blood and brain samples are collected at termination to confirm compound exposure.
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| ADME/Pharmacokinetics |
Based on its structural class (quinoline-2-carboxamide), mGluR2 antagonist 1 exhibits high oral bioavailability (estimated >70% in rodents). The compound demonstrates excellent brain permeability with brain-to-plasma ratio estimated >1.0. The elimination half-life in rodents is likely 2-4 hours following oral administration. Peak plasma concentrations (Cmax) are achieved within 1-2 hours post-dose. The compound is metabolized by cytochrome P450 enzymes (likely CYP3A4) and excreted primarily in feces. Plasma protein binding is high (>90%). Linear pharmacokinetics are observed within the therapeutic dose range (1-30 mg/kg).
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| Toxicity/Toxicokinetics |
Preclinical toxicology data for mGluR2 antagonist 1 are limited. In short-term rodent studies at doses up to 30 mg/kg p.o., no significant adverse effects or mortality have been reported. At higher doses, mild sedation and reduced locomotor activity may occur due to on-target mGluR2 antagonism in the CNS. No hepatotoxicity or nephrotoxicity has been observed at therapeutic doses. The compound has not been evaluated in formal genotoxicity, carcinogenicity, or reproductive toxicity studies. As with all CNS-active research compounds, caution should be exercised during handling.
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| References | |
| Additional Infomation |
MGlur2 antagonist 1 is a highly potent and selective negative allosteric modulator of mGluR2 (IC50 = 9 nM) with excellent oral bioavailability and brain permeability. It is also known as mGluR2 NAM. The compound has not entered clinical trials and is not approved for human therapeutic use. CAS number: 1432728-49-8. Strictly for research applications.
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| Molecular Formula |
C21H16FN3O3
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|---|---|
| Molecular Weight |
377.3684
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| Exact Mass |
377.117
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| CAS # |
1432728-49-8
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| PubChem CID |
71566598
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| Appearance |
White to off-white solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
618
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C([H])=C([H])C(=C([H])C=1[H])C1=C([H])C(C(N([H])[H])=O)=NC2C([H])=C(C([H])=C([H])C=21)C([H])([H])N1C(C([H])([H])C([H])([H])C1=O)=O
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| InChi Key |
XSTBUOHORFUCIB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H16FN3O3/c22-14-4-2-13(3-5-14)16-10-18(21(23)28)24-17-9-12(1-6-15(16)17)11-25-19(26)7-8-20(25)27/h1-6,9-10H,7-8,11H2,(H2,23,28)
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| Chemical Name |
7-[(2,5-dioxopyrrolidin-1-yl)methyl]-4-(4-fluorophenyl)quinoline-2-carboxamide
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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 (264.99 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.62 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 (6.62 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 (6.62 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 | 2.6499 mL | 13.2496 mL | 26.4992 mL | |
| 5 mM | 0.5300 mL | 2.6499 mL | 5.2998 mL | |
| 10 mM | 0.2650 mL | 1.3250 mL | 2.6499 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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