| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Rat mGlu4 290 nM (EC50) Human mGlu4 1.1 μM (EC50) mGlu6 6.8 μM (EC50) mGlu5 17.9 μM (EC50)
mGlu4 (metabotropic glutamate receptor 4). Also exhibits antagonist activity at mGlu5 (IC50 = 17.9 μM) and PAM activity at mGlu6 (IC50 = 6.8 μM); inhibits human MAO-A (Ki = 8.5 μM) and MAO-B (Ki = 0.72 μM). |
|---|---|
| ln Vitro |
VU0364770 hydrochloride exhibits EC50 values of 290 nM and 1.1 μM at rat mGlu4 and human mGlu4 receptors, respectively. It potentiates the response to an EC20 concentration of glutamate in a concentration-dependent manner and shifts the glutamate concentration-response curve 31.4-fold to the left. These data confirm its potent and efficacious PAM activity at mGlu4.
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| ln Vivo |
In preclinical rodent models of Parkinson's disease, VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist. This demonstrates its potential as a novel therapeutic approach for the treatment of Parkinson's disease. Its activity at other targets, such as MAO enzymes, may also contribute to its overall pharmacological profile.
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| Enzyme Assay |
In vitro binding assays are performed to evaluate the affinity of VU0364770 for mGlu4 and other receptors. Radioligand binding studies using membrane preparations from cells expressing human or rat mGlu4 receptors are conducted. The compound's ability to bind to the allosteric site is assessed, although its PAM activity is primarily characterized in functional assays.
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| Cell Assay |
Cells expressing recombinant human or rat mGlu4 receptors are treated with an EC20 concentration of glutamate in the presence of varying concentrations of VU0364770. The potentiation of receptor activity is measured by monitoring downstream signaling pathways, such as calcium mobilization or cAMP inhibition. The EC50 for the PAM effect is determined from the concentration-response curve.
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| Animal Protocol |
In vivo efficacy is assessed in rodent models of Parkinson's disease, such as the 6-hydroxydopamine (6-OHDA)-lesioned rat model or the haloperidol-induced catalepsy model. VU0364770 is typically administered systemically (e.g., i.p. or orally) to evaluate its ability to improve motor function and reduce parkinsonian symptoms. Combination studies with L-DOPA or adenosine A2A antagonists are also performed.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are publicly available for VU0364770 hydrochloride. For systemically active PAMs like this compound, standard PK studies in rodents would be conducted to determine oral bioavailability, half-life, and brain penetration to support in vivo efficacy studies.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for this compound. As a research chemical, its toxicity profile would be evaluated in standard preclinical safety studies. Observed effects are likely related to its mechanism of action as an mGlu4 PAM and its off-target activities, such as MAO inhibition.
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| References | |
| Additional Infomation |
VU0364770 hydrochloride is a systemically active mGlu4 PAM that has shown promise in preclinical models of Parkinson's disease. Its ability to enhance mGlu4 function, either alone or in combination with other therapies, highlights its potential as a novel treatment strategy. It is not approved for human use and is exclusively a research tool. Its off-target activities at mGlu5, mGlu6, and MAO enzymes are also of interest.
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| Molecular Formula |
C12H10CL2N2O
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|---|---|
| Molecular Weight |
269.1266
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| Exact Mass |
268.017
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| CAS # |
1414842-70-8
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| Related CAS # |
VU0364770;61350-00-3
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| PubChem CID |
56587900
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
247
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C([H])C([H])=C([H])C(=C1[H])N([H])C(C1=C([H])C([H])=C([H])C([H])=N1)=O.Cl[H]
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| InChi Key |
CZNNJOSFWZBQKH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H9ClN2O.ClH/c13-9-4-3-5-10(8-9)15-12(16)11-6-1-2-7-14-11;/h1-8H,(H,15,16);1H
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| Chemical Name |
N-(3-chlorophenyl)pyridine-2-carboxamide;hydrochloride
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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: Please store this product in a sealed and protected environment, 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 (371.57 mM)
H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (18.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (18.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7157 mL | 18.5784 mL | 37.1568 mL | |
| 5 mM | 0.7431 mL | 3.7157 mL | 7.4314 mL | |
| 10 mM | 0.3716 mL | 1.8578 mL | 3.7157 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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