| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
VU0424465 targets the mGlu5 receptor, specifically binding to the MPEP allosteric binding site with high affinity (Ki = 11.8 nM). It functions as both a positive allosteric modulator and a partial agonist. The compound exhibits bias towards signaling via IP1 accumulation and ERK1/2 phosphorylation over intracellular calcium (iCa2+) mobilization in HEK293 and neuronal cells.
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| ln Vitro |
In the absence of glutamate, VU0424465 demonstrates strong agonist action and causes calcium mobilization (EC50 = 171 ± 15 nM, with a maximal efficacy of 65% when compared to glutamate) [2]. With an EC50 of 1.5 ± 0.8 nM, VU0424465 increases the mobilization of calcium caused by glutamate[2]. In HEK293A-mGlu5-low cells, VU0424465 shows a strong bias toward iCa2+ mobilization, IP1 accumulation (110-fold), and ERK1/2 phosphorylation (9-fold) [1].
In vitro, VU0424465 exhibits robust agonist activity, inducing calcium mobilization in the absence of glutamate with an EC50 of 171 nM. As a PAM, it potentiates glutamate-induced calcium mobilization with an EC50 of 1.5 nM. It increases the maximum response to glutamate by 30% and activates Gs protein in HEK 293 cells. |
| ln Vivo |
In vivo, VU0424465 induces epileptiform activity in CA3 hippocampal neurons in vitro and convulsions in vivo. This indicates that while it is a valuable tool for studying mGlu5 biology, its potent excitatory effects can lead to significant neurological side effects, highlighting the complex pharmacology of biased mGlu5 modulators.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for VU0424465 are performed using membrane preparations expressing the mGlu5 receptor. Radioligand binding assays are used to determine its affinity for the MPEP allosteric site, yielding a Ki of 11.8 nM. These cell-free systems quantify the compound's binding affinity and allosteric interactions.
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| Cell Assay |
In vitro cellular assays are conducted using HEK293 cells or neuronal cultures expressing mGlu5. Calcium mobilization is measured using fluorescent indicators to assess both the compound's agonist activity (EC50 = 171 nM) and its PAM activity in potentiating glutamate responses (EC50 = 1.5 nM). Signaling bias is determined by measuring IP1 accumulation and ERK1/2 phosphorylation.
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| Animal Protocol |
In vivo animal experiments for VU0424465 are primarily conducted in rodent models to study its effects on neural excitability. Administration of the compound leads to observable convulsions, making it a tool to study the in vivo consequences of mGlu5 activation and biased signaling.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties are not extensively detailed in the literature. The compound has a molecular weight of 326.36 and is soluble in DMSO.
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| Toxicity/Toxicokinetics |
Toxicity is highlighted by its ability to induce epileptiform activity and convulsions, indicating a narrow therapeutic window and significant pro-convulsant potential.
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| References |
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| Additional Infomation |
VU0424465 is a research compound and is not approved for clinical use. It serves as a key pharmacological tool for investigating the unique signaling profiles of mGlu5 PAMs and their implications for in vivo activity.
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| Molecular Formula |
C19H19FN2O2
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|---|---|
| Molecular Weight |
326.364768266678
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| Exact Mass |
326.143
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| CAS # |
1428630-85-6
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| PubChem CID |
53384864
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| Appearance |
White to off-white solid
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
533.8±50.0 °C at 760 mmHg
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| Flash Point |
276.7±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.594
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| LogP |
2.95
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
508
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1=CC=CC(=C1)C#CC1=CN=C(C=C1)C(N[C@H](C)C(C)(C)O)=O
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| InChi Key |
ZPKZAFDYFVJULO-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C19H19FN2O2/c1-13(19(2,3)24)22-18(23)17-10-9-15(12-21-17)8-7-14-5-4-6-16(20)11-14/h4-6,9-13,24H,1-3H3,(H,22,23)/t13-/m1/s1
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| Chemical Name |
5-[2-(3-fluorophenyl)ethynyl]-N-[(2R)-3-hydroxy-3-methylbutan-2-yl]pyridine-2-carboxamide
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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: ~100 mg/mL (~306.4 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (15.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (50.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (15.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 DMSO stock solution (50.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 5 mg/mL (15.32 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 DMSO stock solution (50.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0641 mL | 15.3205 mL | 30.6410 mL | |
| 5 mM | 0.6128 mL | 3.0641 mL | 6.1282 mL | |
| 10 mM | 0.3064 mL | 1.5321 mL | 3.0641 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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