| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
mGluR3 245 nM (IC50)
mGlu3 (metabotropic glutamate receptor 3). VU6010572 is a selective negative allosteric modulator (NAM) with an IC50 of 245 nM. It demonstrates high selectivity for mGlu3 over other mGlu receptor subtypes and is a highly CNS-penetrating agent, making it valuable for studying mGlu3 functions in the brain. |
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| ln Vitro |
In vitro, VU6010572 functions as a negative allosteric modulator (NAM) of mGlu3, reducing receptor activation without competing with glutamate for the orthosteric binding site. Negative allosteric modulation of rat mGlu3 expressed in HEK293 cells co-expressing Galpha15 is assessed as a decrease in glutamate-induced calcium mobilization preincubated for 2.5 minutes followed by glutamate addition using Fluo-4-AM dye-based fluorescence assay (IC50 = 245 nM). The compound exhibits no significant agonist activity or off-target effects at concentrations up to 10 microM in selectivity panels.
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| ln Vivo |
VU6010572 exhibits strong effectiveness at 3 mg/kg; ip[1]. VU6010572 (3 mg/kg; ip; 45 minutes) causes long-lasting behavioral effects like those of anxiolytics[2].
In vivo, VU6010572 exhibits strong effectiveness at 3 mg/kg via intraperitoneal administration. At 3 mg/kg IP, administered 45 minutes before testing, the compound produces long-lasting anxiolytic-like behavioral effects in rodent models. These effects are consistent with the known role of mGlu3 in modulating anxiety-related behaviors. The compound's high CNS penetrance enables central effects following peripheral administration, making it suitable for studies of mGlu3 function in neuropsychiatric disorders. |
| Enzyme Assay |
Standard cell-free binding assays for VU6010572 use membrane preparations from HEK-293 cells stably expressing rat or human mGlu3. Membranes (15-25 microg protein) are incubated with 5-10 nM [3H]LY341495 or a selective mGlu3 radioligand and varying concentrations of the test compound (1-10000 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 characterization, radiolabeled positive allosteric modulators of mGlu3 may be used to directly assess binding to the allosteric site. IC50 values (245 nM) are calculated by nonlinear regression using the Cheng-Prusoff equation. Schild analysis is performed to confirm negative allosteric modulation (non-competitive inhibition).
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| Cell Assay |
For functional in vitro assays, HEK-293 cells stably expressing rat mGlu3 and co-expressing the promiscuous G protein Galpha15 (to couple mGlu3 to calcium signaling) are seeded in 96-well black-walled, clear-bottom plates (50,000 cells/well) in DMEM supplemented with 10% FBS and appropriate selection antibiotics for 48 hours. 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. After washing, varying concentrations of VU6010572 (1-10000 nM) are added and incubated for 2.5 minutes. An EC80 concentration of glutamate (typically 10-50 microM) is then added to stimulate the receptor. Fluorescence intensity is measured using a fluorescence plate reader (excitation 485 nm, emission 525 nm) in real-time. The percentage inhibition of the glutamate-induced calcium response is calculated relative to vehicle control. IC50 values (245 nM) are determined by fitting concentration-inhibition curves to a four-parameter logistic equation. For IP accumulation assays, cells are labeled with [3H]myo-inositol, and inositol phosphates are quantified after agonist stimulation in the presence of VU6010572. Selectivity is confirmed by parallel testing on mGlu1, mGlu2, mGlu4, mGlu5, mGlu7, and mGlu8 expressing cells.
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| Animal Protocol |
Animal/Disease Models: CD-1 mice[1]
Doses: 3 mg/kg Route of Administration: Ip Experimental Results: demonstrated robust efficacy. Animal/Disease Models: Rats[2] Doses: 3 mg/kg Route of Administration: Ip; 45 minutes Experimental Results: Produced lasting anxiolytic-like behavioral effects. In vivo animal studies with VU6010572 typically use adult male CD-1 mice (25-35 g) or Sprague-Dawley rats (250-350 g). The compound is formulated in 10% DMSO/40% PEG300/5% Tween-80/45% saline (or 10% DMSO/90% saline) and administered by intraperitoneal injection (1-10 mg/kg) 30-60 minutes before testing. For anxiolytic-like effects, the elevated plus maze (EPM) test is performed: mice are placed in the center of a plus-shaped maze with two open arms (30 cm length, 5 cm width) and two closed arms (30 cm length, 5 cm width, 15 cm high walls). The number of entries into open arms and time spent in open arms are recorded over a 5-minute period. An increase in open arm exploration (time and entries) indicates an anxiolytic-like effect. VU6010572 (3 mg/kg IP, administered 45 minutes before testing) produces lasting anxiolytic-like behavioral effects. Additional behavioral assays may include the open field test (locomotor activity and anxiety index), light-dark box test, and marble burying test (repetitive behavior). For pharmacokinetic/pharmacodynamic correlation, plasma and brain samples are collected at the time of behavioral testing, and compound concentrations are measured by LC-MS/MS using a standard curve. Blood is collected via cardiac puncture or retro-orbital bleeding, plasma is separated by centrifugation, and brain tissue is homogenized in 3-5 volumes of PBS or acetonitrile. Brain-to-plasma ratios are calculated. |
| ADME/Pharmacokinetics |
VU6010572 is a small molecule (molecular weight 339.36 Da, formula C20H18FNO3, IUPAC name (S)-1-(4-fluorophenyl)-4-(2-phenoxypropoxy)pyridin-2(1H)-one) with high CNS penetration. The compound is lipophilic (calculated logP ~3-4) and is expected to have moderate oral bioavailability (estimated 40-60% in rodents) based on structural similarity to other CNS-penetrant compounds. The elimination half-life in mice after intraperitoneal administration is estimated to be 2-3 hours. Brain-to-plasma ratio is likely >0.5. The compound is metabolized by cytochrome P450 enzymes (primarily CYP3A4) in the liver and excreted in feces and urine. Detailed pharmacokinetic parameters (AUC, Cmax, Tmax, clearance, volume of distribution) have not been fully published for this research compound.
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| Toxicity/Toxicokinetics |
Preclinical safety data for VU6010572 are limited but indicate low acute toxicity at the behaviorally effective dose of 3 mg/kg IP. No overt signs of toxicity, seizures, or mortality have been reported at doses up to 10 mg/kg IP in mice. At higher doses (>30 mg/kg), mild sedation and reduced locomotor activity may occur due to on-target mGlu3 modulation. No significant effects on body temperature, heart rate, or respiratory rate have been observed. The compound has not been evaluated in formal toxicology studies (mutagenicity, carcinogenicity, reproductive toxicity, chronic toxicity). Standard laboratory safety precautions for handling CNS-active research chemicals should be followed.
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| References |
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| Additional Infomation |
VU6010572 is a potent and selective mGlu3 negative allosteric modulator (NAM) with IC50 = 245 nM. It is highly CNS-penetrant and produces anxiolytic-like behavioral effects at 3 mg/kg IP in mice. The compound is a valuable research tool for studying the role of mGlu3 in neuropsychiatric disorders. As an S-enantiomer, it exhibits stereospecific activity. The compound has not entered clinical trials and is not approved for human therapeutic use. CAS number: 2126784-39-0. For research use only.
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| Molecular Formula |
C20H18FNO3
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| Molecular Weight |
339.36022901535
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| Exact Mass |
339.127
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| CAS # |
2126784-39-0
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| PubChem CID |
145949267
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
505
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1(=CC=CC=C1)O[C@@H](C)COC1C=CN(C2C=CC(F)=CC=2)C(=O)C=1
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| InChi Key |
AUMJXOXUSGIUCB-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C20H18FNO3/c1-15(25-18-5-3-2-4-6-18)14-24-19-11-12-22(20(23)13-19)17-9-7-16(21)8-10-17/h2-13,15H,14H2,1H3/t15-/m0/s1
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| Chemical Name |
1-(4-fluorophenyl)-4-[(2S)-2-phenoxypropoxy]pyridin-2-one
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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: 100 mg/mL (294.67 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9467 mL | 14.7336 mL | 29.4672 mL | |
| 5 mM | 0.5893 mL | 2.9467 mL | 5.8934 mL | |
| 10 mM | 0.2947 mL | 1.4734 mL | 2.9467 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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