2. GPCR/G Protein Neuronal Signaling
  3. mGluR
  4. VU0364770

VU0364770 is a selective and potent positive allosteric modulator (PAM) of mGlu4. VU0346770 exhibits EC50s of 290 nM and 1.1 μM at rat mGlu4 and human mGlu4 receptor, respectively. VU0364770 exhibits antagonist activity at mGlu5 with a potency of 17.9 μM and PAM activity at mGlu6 with a potency of 6.8 μM. VU0364770 also possesses activity at MAO with Ki values of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively.

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VU0364770 Chemical Structure

VU0364770 Chemical Structure

CAS No. : 61350-00-3

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Based on 1 publication(s) in Google Scholar

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VU0364770 Related Antibodies

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  • Biological Activity

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  • Purity & Documentation

  • References

  • Customer Review

Description

VU0364770 is a selective and potent positive allosteric modulator (PAM) of mGlu4. VU0346770 exhibits EC50s of 290 nM and 1.1 μM at rat mGlu4 and human mGlu4 receptor, respectively. VU0364770 exhibits antagonist activity at mGlu5 with a potency of 17.9 μM and PAM activity at mGlu6 with a potency of 6.8 μM. VU0364770 also possesses activity at MAO with Ki values of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively[1].

IC50 & Target[1]

Rat mGlu4

290 nM (EC50)

Human mGlu4

1.1 μM (EC50)

mGlu6

6.8 μM (EC50)

mGlu5

17.9 μM (EC50)

In Vitro

VU0364770 is a selective positive allosteric modulator of mGlu4 in recombinant systems. VU0364770 is a potent PAM of multiple signaling pathways that enhances the response of the rat and human mGlu4 receptors to the endogenous agonist glutamate. VU0364770 produces a concentration-dependent potentiation of the response to an EC20 concentration of glutamate with EC50 of 1.1±0.2 μM and increases the maximal response to glutamate from 100 to 227±17%. Because of concerns that this chemical scaffold might possess activity at MAO, full IC50 determinations is performed for VU0364770 at the MAO-A and MAO-B isoforms; these studies result in Kis of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively. When tested at a 10 μM concentration at each mGlu receptor, VU0364770 exhibits weak PAM activity (4.3-fold left shift of the glutamate CRC) at mGlu6 and antagonist activity (3.3-fold right shift of the glutamate CRC) at mGlu5 (compare to the 16.5-fold left shift of the glutamate concentration-response for mGlu4 at 10 μM). When further evaluated in a full concentration-response curve format, VU0364770 exhibits antagonist activity at mGlu5 with a potency of 17.9±5.5 μM and PAM activity at mGlu6 with a potency of 6.8±1.7 μM (compare with the potency of VU0364770 on the rat mGlu4 receptor of 290±80 nM)[1].

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

VU0364770 Related Antibodies
In Vivo

VU0364770 exhibits suitable pharmacokinetic properties for systemic dosing in animal models. After intravenous administration, VU0364770 is rapidly clears from the systemic circulation (165 ml/min/kg) and exhibits a volume of distribution of 2.92 L/kg. VU0364770 is a highly protein-bound ligand displaying free fractions of 2.7 and 1.8% in human and rat plasma, respectively. VU0364770 also shows an improved pharmacokinetic profile relative to previously reported mGlu4 PAMs with enhanced central penetration and a total brain-to-plasma ratio of more than 1 after systemic administration of a 10 mg/kg dose. VU0364770 produces a dose-dependent reversal of haloperidol-induced catalepsy. VU0364770 dose-dependently reverses haloperidol (0.75 mg/kg)-induced catalepsy in rats, significant at doses of 10 to 56.6 mg/kg, after subcutaneous dosing (F6,69=8.04; p<0.001)[1].

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

232.67

Formula

C12H9ClN2O
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

O=C(C1=NC=CC=C1)NC2=CC=CC(Cl)=C2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : ≥ 100 mg/mL (429.79 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 4.2979 mL 21.4897 mL 42.9793 mL
5 mM 0.8596 mL 4.2979 mL 8.5959 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Concentration
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Volume
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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Volume (start)

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C2

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Volume (final)

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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    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (10.74 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

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

    Solubility: ≥ 2.5 mg/mL (10.74 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 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 (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

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

Dosage

mg/kg

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(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
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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
References
Kinase Assay
[1]

The effects of VU0364770 on rat mGlu1 and mGlu5 are assessed by using calcium mobilization and measuring the glutamate concentration-response relationship in the presence and absence of 10 μM VU0364770. Using a double-addition protocol, VU0364770 is added to the cells, followed 2.5 min later by a full concentration-response of glutamate. Shifts of the concentration-response relationship are used to assess potential potentiator (left shift of more than 2-fold) or antagonist (right shift of more than 2-fold or depression of the maximum response by at least 75%) activity of VU0364770. Compounds are further assessed for mGlu5 antagonist activity by performing a full concentration-response curve, starting at 30 μM and serially diluted it by using 1:3 dilutions, in the presence of an EC80 concentration of glutamate[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Rats[1]
Adult male Sprague-Dawley rats, weighing 250 to 300 g, are used. Rat are examined for catalepsy 30 min after the administration of either VU0364770 (1-56.6 mg/kg s.c.), VU0364772 (1-56.6 mg/kg s.c.), A2A antagonist (56.6 mg/kg p.o.), Preladenant (0.03-30 mg/kg p.o.), or vehicle. In the interaction studies rats ate administered VU0364770 (10 or 30 mg/kg) + vehicle, VU0364770 (10 or 30 mg/kg)+Preladenant (0.1-1 mg/kg), or vehicle+Preladenant (0.1-1 mg/kg) 30 min before testing.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 4.2979 mL 21.4897 mL 42.9793 mL 107.4483 mL
5 mM 0.8596 mL 4.2979 mL 8.5959 mL 21.4897 mL
10 mM 0.4298 mL 2.1490 mL 4.2979 mL 10.7448 mL
15 mM 0.2865 mL 1.4326 mL 2.8653 mL 7.1632 mL
20 mM 0.2149 mL 1.0745 mL 2.1490 mL 5.3724 mL
25 mM 0.1719 mL 0.8596 mL 1.7192 mL 4.2979 mL
30 mM 0.1433 mL 0.7163 mL 1.4326 mL 3.5816 mL
40 mM 0.1074 mL 0.5372 mL 1.0745 mL 2.6862 mL
50 mM 0.0860 mL 0.4298 mL 0.8596 mL 2.1490 mL
60 mM 0.0716 mL 0.3582 mL 0.7163 mL 1.7908 mL
80 mM 0.0537 mL 0.2686 mL 0.5372 mL 1.3431 mL
100 mM 0.0430 mL 0.2149 mL 0.4298 mL 1.0745 mL
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VU0364770 Related Classifications

Help & FAQs
  • 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:

VU036477061350-00-3VU 0364770VU-0364770mGluRMetabotropic glutamate receptorsInhibitorinhibitorinhibit

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