| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
VU0422288 targets group III metabotropic glutamate receptors, specifically mGlu4, mGlu7, and mGlu8. These receptors are G protein-coupled receptors that play important roles in modulating synaptic transmission and neuronal excitability in the central nervous system. As a positive allosteric modulator, VU0422288 enhances the activity of these receptors.
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| ln Vitro |
In coronal slices containing the hippocampus, Vu0422288 (1 μM; 5 min) potentiates the reduction in field excitatory postsynaptic potentials (fEPSPs) elicited by 30 μM LSP4-2022 [1]. In Mecp2-/y slices, VU0422288 (1 μM; 10 min) by itself is unable to alter the slope of fEPSP, suggesting that mGlu7 lacks reinforcing action in stimulating conditions [2].
VU0422288 is a potent positive allosteric modulator of group III mGlu receptors with EC50 values of 108, 125, and 146 nM for mGlu4, mGlu8, and mGlu7, respectively. In hippocampal slices, VU0422288 potentiates the reduction in field excitatory postsynaptic potentials elicited by a group III mGlu agonist. It has no effect on its own in Mecp2-/y slices. |
| ln Vivo |
Animal VU0422288 (10 mg/kg; i.p.; single dose) has a Sprague-Dawley neural/brain partitioning factor of 1.67 in the cohort, with predicted free brain concentrations of approximately 40 nM. In contrast, VU0422288 (30 mg/kg; i.p.; once daily for 17 days) rescued synaptic plasticity defects and learning and memory phenotypes and reduced apnea frequency in Mecp2+/- mice. 】.
VU0422288 rescues synaptic plasticity defects and learning and memory phenotypes in Mecp2+/- mice, a model of Rett syndrome. It also reduces apnea frequency in these mice. The compound has a brain partitioning factor of 1.67, with predicted free brain concentrations of approximately 40 nM. |
| Enzyme Assay |
VU0422288 is evaluated in cell-free receptor binding assays to determine its affinity for group III mGlu receptors. Radioligand binding displacement assays are performed using membrane preparations expressing mGlu receptor subtypes. Competition binding experiments are conducted with increasing concentrations of VU0422288 and a fixed concentration of a labeled reference ligand.
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| Cell Assay |
VU0422288 is assessed in cell-based functional assays to measure its modulatory activity at group III mGlu receptors. Cells expressing mGlu4, mGlu7, or mGlu8 are treated with VU0422288, and receptor activity is measured by assessing downstream signaling pathways, such as calcium mobilization or GTPγS binding. EC50 values are determined.
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| Animal Protocol |
VU0422288 is administered intraperitoneally in animal models to evaluate its effects on group III mGlu receptor-mediated functions. It has been studied in models of Rett syndrome, where it rescues synaptic plasticity defects and learning and memory phenotypes at a dose of 30 mg/kg once daily for 17 days. It also reduces apnea frequency.
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| ADME/Pharmacokinetics |
VU0422288 has a molecular weight of 360.19 and a molecular formula of C17H11Cl2N3O2. It has a CAS number of 1630936-95-6. The compound is soluble in DMSO. It should be stored as a powder at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is available for VU0422288. The compound is for research use only and is not intended for human therapeutic use. Its safety profile has not been extensively characterized in the available literature.
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| References |
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| Additional Infomation |
Positive allosteric regulator of metabolic glutamate receptor 7; structure described in the first article.
VU0422288 is a novel and potent positive allosteric modulator of group III mGlu receptors. It is also known as ML-396. The compound has a CAS number of 1630936-95-6. It is a CNS-penetrant compound used as a research tool to study the role of group III mGlu receptors in synaptic plasticity, learning, memory, and various neurological disorders such as Rett syndrome. It is not approved for clinical use. |
| Molecular Formula |
C17H11CL2N3O2
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|---|---|
| Molecular Weight |
360.194
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| Exact Mass |
359.022
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| CAS # |
1630936-95-6
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| PubChem CID |
73058507
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
422.6±45.0 °C at 760 mmHg
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| Flash Point |
209.4±28.7 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.671
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| LogP |
3.51
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
427
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=NC(=C1)C(=O)NC2=CC(=C(C=C2)OC3=NC=C(C=C3)Cl)Cl
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| InChi Key |
MZRLPXFGQKQHST-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11Cl2N3O2/c18-11-4-7-16(21-10-11)24-15-6-5-12(9-13(15)19)22-17(23)14-3-1-2-8-20-14/h1-10H,(H,22,23)
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| Chemical Name |
N-[3-chloro-4-(5-chloropyridin-2-yl)oxyphenyl]pyridine-2-carboxamide
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| Synonyms |
VU 0422288 VU-0422288 VU0422288
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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) |
DMSO : ~25 mg/mL (~69.41 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.94 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 25.0 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 | 2.7763 mL | 13.8816 mL | 27.7631 mL | |
| 5 mM | 0.5553 mL | 2.7763 mL | 5.5526 mL | |
| 10 mM | 0.2776 mL | 1.3882 mL | 2.7763 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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