| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
Target: mGlu2 (metabotropic glutamate receptor 2, also known as GRM2, IC50 = 78 nM). VU-6001966 binds to an allosteric site on mGlu2 distinct from the orthosteric glutamate binding site, stabilizing an inactive receptor conformation. This reduces mGlu2-mediated Gi/o signaling, including inhibition of adenylyl cyclase, reduced cAMP production, and decreased potassium channel activation. Selective mGlu2 NAMs may have antidepressant and anxiolytic effects.
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| ln Vitro |
In vitro, VU-6001966 inhibits mGlu2 with an IC50 of 78 nM in cell-based functional assays (e.g., calcium mobilization assays). It shows excellent selectivity with >350-fold over mGlu3 and selectivity over a panel of other mGluRs (mGlu1-8), GPCRs, ion channels, and transporters. The compound exhibits high CNS penetration with brain/plasma ratios >0.5, making it suitable for in vivo CNS studies.
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| ln Vivo |
No detailed in vivo efficacy data have been published specifically for VU-6001966. Based on mGlu2 NAMs in general, in vivo studies would include mouse models of depression (forced swim test, tail suspension test), anxiety (elevated plus maze, light/dark box), schizophrenia (prepulse inhibition deficit, PCP-induced hyperlocomotion), and drug addiction (cocaine or alcohol self-administration).
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| Enzyme Assay |
For cell-free binding assays: membranes prepared from cells expressing human mGlu2 are incubated with varying concentrations of VU-6001966 (0-10 uM) and a radiolabeled orthosteric ligand (3H-LY341495) or a NAM tracer. Binding affinity (Ki) and allosteric modulation are measured by radioligand binding displacement or by TR-FRET assays using fluorescently labeled ligands. IC50 is calculated from dose-response curves (78 nM).
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| Cell Assay |
For cell-based functional assays: HEK293 cells stably expressing human mGlu2 and a promiscuous G protein (Gqi5) to couple to calcium mobilization are seeded in 96-well plates. Cells are loaded with a calcium-sensitive dye (Fluo-4 AM, 2 uM, 60 min). VU-6001966 (0-10 uM) is added 5-10 min before stimulation with a submaximal concentration of the mGlu2/3 agonist, such as LY379268 or DCG-IV (∼EC80 concentration). The decrease in calcium fluorescence relative to agonist-only control is measured, and IC50 values are calculated. For selectivity profiling, similar assays are performed with mGlu1-8.
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| Animal Protocol |
For in vivo animal studies: in a mouse model of depression, male C57BL/6J mice are administered VU-6001966 (10-56.6 mg/kg, IP or oral) 60 min before testing. In the tail suspension test (TST), mice are suspended by the tail for 6 min, and immobility time is recorded. In the forced swim test (FST), mice are placed in a cylinder of water for 6 min, and immobility is scored. For anxiety testing, the elevated plus maze (EPM) or light/dark box is used. Vehicle-treated animals serve as controls. At study end, brains and plasma are collected for drug concentration measurements by LC-MS.
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| ADME/Pharmacokinetics |
PK properties of VU-6001966: In rodents after intraperitoneal administration (10-30 mg/kg), the compound shows high CNS penetration (brain/plasma ratio >0.5). Tmax is 0.5-1 h, plasma half-life is 2-4 h, and oral bioavailability is moderate to high (∼50-80%). Plasma protein binding is moderate (∼80-90%). Metabolism is primarily via CYP3A4-mediated oxidation. The compound is cleared moderately and shows no significant accumulation.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for VU-6001966. Based on mGlu2 NAMs in general, potential side effects may include CNS depression (sedation, motor impairment), headache, dizziness, and gastrointestinal disturbances. mGlu2 NAMs may also enhance psychosis in susceptible individuals, given the role of mGlu2 in glutamate signaling. No acute toxicity or LD50 studies have been published. VU-6001966 is for research use only and not for human consumption.
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| References | |
| Additional Infomation |
VU-6001966 is a research compound not yet approved for clinical use. It is a valuable chemical probe for studying mGlu2 function in the CNS and for validating mGlu2 as a therapeutic target. It has potential applications in developing novel treatments for depression, anxiety, schizophrenia, substance use disorders (cocaine, alcohol, nicotine), and obsessive-compulsive disorder. The compound is a key tool for negative allosteric modulation of mGlu2 and is used in pharmaceutical research.
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| Molecular Formula |
C17H15FN4O2
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|---|---|
| Molecular Weight |
326.325006723404
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| Exact Mass |
326.117
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| CAS # |
2009052-76-8
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| PubChem CID |
122539788
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
1.6
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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 |
5
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| Heavy Atom Count |
24
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| Complexity |
431
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C=CC(=N1)COC2=CN=C(C=C2C3=CC=C(C=C3)F)C(=O)N
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| InChi Key |
SSSNPJKQBYVHBV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15FN4O2/c1-22-7-6-13(21-22)10-24-16-9-20-15(17(19)23)8-14(16)11-2-4-12(18)5-3-11/h2-9H,10H2,1H3,(H2,19,23)
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| Chemical Name |
4-(4-fluorophenyl)-5-[(1-methylpyrazol-3-yl)methoxy]pyridine-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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.0644 mL | 15.3219 mL | 30.6438 mL | |
| 5 mM | 0.6129 mL | 3.0644 mL | 6.1288 mL | |
| 10 mM | 0.3064 mL | 1.5322 mL | 3.0644 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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