2. GPCR/G Protein Neuronal Signaling Metabolic Enzyme/Protease
  3. mGluR Cytochrome P450
  4. VU6001966

VU6001966 is a brain-penetrant and selective mGlu2 receptor inhibitor. VU6001966 blocks mGlu2 receptor activity, counteracts LY379268 (HY-103558)-mediated blood-brain barrier protection and inflammatory cytokine dampening in microglia under inflammatory conditions. VU6001966 enhances antidepressant effects when combined with Scopolamine (HY-N0296). VU6001966 can be used for the research of major depressive disorder.

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VU6001966

VU6001966 Chemical Structure

CAS No. : 2009052-76-8

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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Based on 1 publication(s) in Google Scholar

VU6001966 Related Antibodies

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CYP1 CYP2 CYP3 CYP4 CYP11 CYP17 Aromatase/CYP19A1 CYP26 CYP51 CYP1A2 CYP2D6 CYP2C9 CYP2C19 CYP3A CYP3A4 CYP17A1

  • Biological Activity

  • Purity & Documentation

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  • Customer Review

Description

VU6001966 is a brain-penetrant and selective mGlu2 receptor inhibitor. VU6001966 blocks mGlu2 receptor activity, counteracts LY379268 (HY-103558)-mediated blood-brain barrier protection and inflammatory cytokine dampening in microglia under inflammatory conditions. VU6001966 enhances antidepressant effects when combined with Scopolamine (HY-N0296). VU6001966 can be used for the research of major depressive disorder[1][2][3][4].

IC50 & Target[4]

mGluR2

78 nM (IC50)

mGluR3

>30 μM (IC50)

CYP1A2

3.1 μM (IC50)

In Vitro

VU6001966 (3 μM; 24-36 h) does not interfere with the protective effects of LY379268 on TNF-α&IFNγ (T&I)-impaired blood-brain barrier properties, including permeability, TEER, tight junction protein localization in TY-10 human brain microvascular endothelial cell monocultures and permeability, TEER, and claudin-5 expression in TY-10 human brain microvascular endothelial + hAST human astrocyte co-cultures[1].
VU6001966 (3 μM; 36 h) significantly attenuates the protective effects of LY379268 on T&I-impaired blood-brain barrier permeability and claudin-5 expression in TY-10 human brain microvascular endothelial + hAST human astrocyte + HMC3 human microglial triple co-cultures[1].
VU6001966 (3 μM; 5 h) significantly reverses the anti-inflammatory effects of LY379268 on T&I-induced cytokine/chemokine expression and blocks the LY379268-induced increase in BDNF expression in HMC3 human microglial cell monocultures[1].
VU6001966 potently inhibits rmGlu2 in rmGlu2/TREx/Ga15-HEK cells with an IC50 of 78 nM and shows no activity against rmGlu3 in rmGlu3/TREx/Ga15-HEK cells at concentrations up to 30 μM[4].
VU6001966 does not inhibit CYP3A4, CYP2D6, or CYP2C9 at concentrations up to 30 μM, but inhibits CYP1A2 with an IC50 of 3.1 μM[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

VU6001966 Related Antibodies

Real Time qPCR[1]

Cell Line: human microglial (HMC3) monocultures
Concentration: 3 μM
Incubation Time: 5 h
Result: Significantly reversed the LY379268-induced reduction in T&I-increased IL-6, IL-1β, and CCL2 mRNA expression.
Significantly blocked the LY379268-induced increase in BDNF mRNA expression in resting microglia.
In Vivo

VU6001966 (1-10 mg/kg; i.p.; daily; 4 days) treatment dose-dependently alleviates stress-induced anhedonia- and apathy-like behaviors in mice[2].
VU6001966 (1 mg/kg; i.p.; daily; 4 days) and Scopolamine alleviates UCMS-induced anhedonia- and apathy-like behaviors in mice without affecting non-stressed animals[2].
Coadministration of VU6001966 (1 mg/kg; i.p.; daily; 4 days) and Scopolamine produces antidepressant-like effects in UCMS-exposed mice that are not blocked by AMPA receptor antagonism, without impairing locomotor activity[2].
Coadministration of VU6001966 (1 mg/kg; i.p.; daily; 4 days) and Scopolamine produces antidepressant-like effects in UCMS-exposed mice that are dependent on TrkB receptor activation, without impairing locomotor activity[2].
Coadministration of VU6001966 (1 mg/kg; i.p.; daily; 4 days) and Scopolamine reverses UCMS-induced deficits in TrkB phosphorylation in the mouse prefrontal cortex[2].
Coadministration of VU6001966 (1 mg/kg; i.p.; daily; 4 days) and Scopolamine does not significantly reverse UCMS-induced impairments in mPFC glutamatergic transmission or synaptic plasticity in mice[2].
Coadministration of VU6001966 (1 mg/kg; i.p.; daily; 4 days) and Scopolamine does not impair spatial or non-spatial cognitive function in either non-stressed or UCMS-exposed mice[2].
VU6001966 (1-10 mg/kg; i.p.; single dose) exerts dose-dependent antidepressant-like effects in the rat forced swim test, with the 10 mg/kg dose significantly reducing immobility time without affecting locomotor activity[3].
VU6001966 (3 mg/kg; i.p.; single dose) significantly enhances antidepressant-like effects in the rat forced swim test, reducing immobility and increasing climbing behavior when coadministered with Scopolamine[3].
VU6001966 (3 mg/kg; i.p.; single dose) modulates frontal cortex neurotransmitter levels in freely moving rats, increasing serotonin and dopamine while decreasing glutamate, and enhances Scopolamine-induced elevations of these neurotransmitters when coadministered with Scopolamine[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6J (male, 6-7 weeks old, 23-25 g, unpredictable chronic mild stress model)[2]
Dosage: 1 mg/kg; 3 mg/kg; 10 mg/kg
Administration: i.p.; daily; 4 days
Result: Dose-dependently alleviated UCMS-induced depressive-like behaviors.
Significantly increased grooming time in the splash test (P = 0.0423) at 3 mg/kg compared to vehicle-treated UCMS mice.
Significantly increased grooming time (P < 0.0001) and sucrose preference (P < 0.0001) at 10 mg/kg compared to vehicle-treated UCMS mice.
Did not affect immobility time in the tail suspension test at 10 mg/kg.
Showed no significant effect on any measured behavioral parameter at 1 mg/kg.
Animal Model: C57BL/6J (male, 6-7 weeks old, 23-25 g, unpredictable chronic mild stress model)[2]
Dosage: 1 mg/kg
Administration: i.p.; daily; 4 days
Result: Significantly reversed UCMS-induced reductions in grooming time in the splash test (P < 0.0001) and sucrose preference in the sucrose preference test (P = 0.0044) compared to vehicle-treated UCMS mice.
Had no effect in non-stressed mice.
Did not significantly affect immobility time in the tail suspension test in either UCMS or non-stressed mice.
Significantly increased grooming time in the splash test (P = 0.0019) and decreased immobility time in the tail suspension test (P = 0.0235) compared to vehicle-treated UCMS mice.
Did not significantly affect locomotor activity at any time point compared to vehicle-treated UCMS mice.
Significantly increased grooming time in the splash test (P = 0.0007) and decreased immobility time in the tail suspension test (P = 0.0039) compared to vehicle-treated UCMS mice.
Had no significant effect on sucrose preference in the sucrose preference test in UCMS mice.
Did not significantly affect locomotor activity at any time point compared to vehicle-treated UCMS mice.
Significantly reversed UCMS-induced reductions in the phospho-TrkB(Tyr816)/TrkB ratio in the PFC (P = 0.0492) compared to vehicle-treated UCMS mice.
Did not significantly affect peEF2/eEF2, pmTOR/mTOR, or BDNF levels in the PFC, nor any measured protein ratios or levels in the hippocampus.
Did not significantly reverse UCMS-induced increases in FP amplitude or UCMS-induced decreases in LTP amplitude in the mPFC, though a non-significant trend toward alleviating the FP amplitude increase was observed.
Did not significantly affect sEPSC frequency or amplitude in either UCMS or non-stressed mice.
Did not significantly affect moved object investigation time in the OLT or novel object investigation time in the NORT in either UCMS or non-stressed mice, indicating no impairment of spatial or non-spatial cognitive function.
Animal Model: Sprague-Dawley (male, 250-350 g)[3]
Dosage: 1 mg/kg; 3 mg/kg; 10 mg/kg
Administration: i.p.; single dose
Result: Induced a dose-dependent reduction in immobility time in the forced swim test.
Produced a statistically significant decrease in immobility time at 10 mg/kg (P = 0.037 vs. vehicle).
Had no effect on immobility, climbing, or swimming times at 1 mg/kg and 3 mg/kg.
Did not alter spontaneous locomotor activity at 3 mg/kg.
Animal Model: Sprague-Dawley (male, 250-350 g)[3]
Dosage: 3 mg/kg
Administration: i.p.; single dose
Result: Produced a significant decrease in immobility time (F(1,22) = 4.35, P = 0.049) compared to individual treatments or vehicle.
Produced a significant increase in climbing time (F(1, 26) = 11.00, P = 0.003) compared to individual treatments or vehicle.
Animal Model: Sprague-Dawley (male, 250-350 g)[3]
Dosage: 3 mg/kg
Administration: i.p.; single dose
Result: Elevated extracellular serotonin levels to approximately 300% of baseline, dopamine levels to approximately 200% of baseline, and decreased extracellular glutamate levels when administered alone.
Had no effect on GABA levels when administered alone.
Elevated serotonin levels to approximately 400% of baseline, dopamine levels to approximately 400% of baseline, glutamate levels to approximately 220% of baseline when coadministered with Scopolamine 0.3 mg/kg.
Had no significant effect on GABA levels compared to control when coadministered with Scopolamine 0.3 mg/kg.
Molecular Weight

326.33

Formula

C17H15FN4O2
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C(C1=NC=C(OCC2=NN(C)C=C2)C(C3=CC=C(F)C=C3)=C1)N
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 10 mg/mL (30.64 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 1 mg/mL (3.06 mM); Clear solution

    This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.89%

SDS (251 KB)

COA (249 KB) HNMR (268 KB) LCMS (104 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.0644 mL 15.3219 mL 30.6438 mL 76.6096 mL
5 mM 0.6129 mL 3.0644 mL 6.1288 mL 15.3219 mL
10 mM 0.3064 mL 1.5322 mL 3.0644 mL 7.6610 mL
15 mM 0.2043 mL 1.0215 mL 2.0429 mL 5.1073 mL
20 mM 0.1532 mL 0.7661 mL 1.5322 mL 3.8305 mL
25 mM 0.1226 mL 0.6129 mL 1.2258 mL 3.0644 mL
30 mM 0.1021 mL 0.5107 mL 1.0215 mL 2.5537 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

VU60019662009052-76-8VU 6001966VU-6001966mGluRCytochrome P450Metabotropic glutamate receptorsCYPsrat frontal cortexTY-10 human brain microvascular endothelial cellsHMC3 human microglial cellshAST human astrocytesTrkB receptorrmGlu2/TREx/Ga15-HEK cellsmajor depressive disorderblood-brain barriermGlu2 receptormicrogliaInhibitorinhibitorinhibit

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