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

VU0364770 

Cat. No.: HY-100588 Purity: 99.57%
Handling Instructions

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.

For research use only. We do not sell to patients.

VU0364770 Chemical Structure

VU0364770 Chemical Structure

CAS No. : 61350-00-3

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Customer Review

Based on 1 publication(s) in Google Scholar

Other Forms of VU0364770:

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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].

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].

Molecular Weight

232.67

Formula

C₁₂H₉ClN₂O

CAS No.

61350-00-3

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 6 months
  -20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : ≥ 100 mg/mL (429.79 mM)

*"≥" 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
10 mM 0.4298 mL 2.1490 mL 4.2979 mL
*Please refer to the solubility information to select the appropriate solvent.
In Vivo:
  • 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

  • 2.

    Add each solvent one by one:  10% DMSO    90% corn oil

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

*All of the co-solvents are provided by MCE.
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
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Keywords:

VU0364770VU 0364770VU-0364770mGluRMetabotropic glutamate receptorsInhibitorinhibitorinhibit

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VU0364770
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