| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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Purity: ≥98%
| Targets |
VU 0364439 targets the metabotropic glutamate receptor 4 (mGlu4), a Group III GPCR. It acts as a positive allosteric modulator (PAM) with an EC50 value of 19.8 nM. By binding to an allosteric site on the receptor, it enhances the receptor's response to glutamate, the endogenous agonist. This modulation of mGlu4 activity is implicated in the regulation of neurotransmission and has potential therapeutic applications in Parkinson's disease, anxiety, and pain.
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| ln Vitro |
VU 0364439 is a mGlu4 (metabotropic glutamate receptor 4) positive allosteric modulator (PAM) with EC50 value of 19.8 nM. VU 0364439 possessed less favorable pharmacokinetic properties. The properties of VU 0364439 prevents VU 0364439 itself from being used as an in vivo tool, but VU 0364439 might inform the mGlu4 community with more in vitro tool compounds. The activation of the mGlu4 receptor, either with an orthosteric agonist or a positive allosteric modulator (PAM), provides impactful interventions in diseases such as Parkinsons disease, anxiety, and pain. mGlu4 PAMs may have several advantages over mGlu4 agonists for a number of reasons.
Kinase Assay: VU 0364439 is a mGlu4 (metabotropic glutamate receptor 4) positive allosteric modulator (PAM) with EC50 value of 19.8 nM. Cell Assay: VU 0364439 exhibited excellent in vitro maximal response and potency relative to another PAM, (−)-PHCCC (a partially selective mGlu4 potentiator, its chemical structure could be found in reference 4). Starting at 30µM, using a 1:3 serial dilutions, VU 0364439 was tested in triplicate. The entire test was performed on one day. Finally, the % (−)-PHCCC value of VU 0364439 was 102.3. The value of % (−)-PHCCC was computed through dividing the maximal response elicited by VU 0364439 by the response of the control PAM, (−)-PHCCC, on the same day. It was also found that the EC50 value of VU 0364439 was 19.8 nM at human mGlu4 In vitro, VU 0364439 is a mGlu4 positive allosteric modulator (PAM) with an EC50 of 19.8 nM. It is a synthetic small-molecule PAM. Its activity has been characterized in cell-based assays using cells expressing human mGlu4. These in vitro studies confirm its mechanism as an mGlu4 PAM. However, its use as an in vivo tool is limited by its less than ideal pharmacokinetic properties. |
| ln Vivo |
VU 0364439 possess less than ideal PK properties preventing their use as in vivo tools. It shows better stability in HLM (63% remaining) than RLM (2% remaining). |
| Enzyme Assay |
Non-cellular binding assays for VU 0364439 typically involve measuring its affinity for the mGlu4 receptor. These assays use membrane preparations from cells expressing the receptor and measure the displacement of a labeled ligand or the enhancement of agonist binding. The compound's ability to modulate receptor activity is assessed by determining the EC50 for potentiation of glutamate-induced signaling. Such assays are essential for characterizing its mechanism as a PAM.
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| Cell Assay |
In vitro cell-based assays for VU 0364439 are conducted using cells expressing mGlu4 to assess its effects on receptor activity. Cells are treated with the compound, and changes in intracellular calcium levels or other downstream signaling pathways are measured. The compound's ability to potentiate glutamate-induced signaling is assessed. These experiments are crucial for confirming its mechanism as a positive allosteric modulator.
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| Animal Protocol |
In vivo animal studies for VU 0364439 are limited due to its less than ideal pharmacokinetic properties. Its poor stability in rat liver microsomes and limited brain penetration prevent its use as an in vivo tool. Further optimization of its pharmacokinetic properties would be required for in vivo applications.
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| ADME/Pharmacokinetics |
VU 0364439 has a molecular weight of 422.29 g/mol. It is a synthetic small molecule. It shows better stability in human liver microsomes (HLM, remaining 63%) compared to rat liver microsomes (RLM, remaining 2%). Its less than ideal pharmacokinetic properties prevent its use as an in vivo tool.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for VU 0364439 are limited, as it is a research compound. It is intended for laboratory use only and is not for human consumption. As with all research chemicals, appropriate safety precautions should be taken when handling VU 0364439.
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| References |
Bioorg Med Chem Lett.2010 Sep 1;20(17):5175-8;J Med Chem.2011 Jul 28;54(14):5070-81.
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| Additional Infomation |
VU 0364439 is a synthetic small-molecule positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGlu4) with an EC50 of 19.8 nM. It is implicated in Parkinson's disease, anxiety, and pain modulation. Its less than ideal pharmacokinetic properties prevent its use as an in vivo tool. VU 0364439 is not an approved drug and is available as a research compound.
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| Molecular Formula |
C18H13CL2N3O3S
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| Molecular Weight |
422.29
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| Exact Mass |
421.005
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| Elemental Analysis |
C, 51.20; H, 3.10; Cl, 16.79; N, 9.95; O, 11.37; S, 7.59
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| CAS # |
1246086-78-1
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| Related CAS # |
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| PubChem CID |
46934289
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.686
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| LogP |
3.82
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
614
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=NC=CC=C1)NC2=CC=C(S(=O)(NC3=CC=CC=C3Cl)=O)C(Cl)=C2
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| InChi Key |
IXHCGJXBIHHIEF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H13Cl2N3O3S/c19-13-5-1-2-6-15(13)23-27(25,26)17-9-8-12(11-14(17)20)22-18(24)16-7-3-4-10-21-16/h1-11,23H,(H,22,24)
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| Chemical Name |
N-[3-chloro-4-[(2-chlorophenyl)sulfamoyl]phenyl]pyridine-2-carboxamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.92 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 25.0 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: ≥ 2.5 mg/mL (5.92 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 | 2.3680 mL | 11.8402 mL | 23.6804 mL | |
| 5 mM | 0.4736 mL | 2.3680 mL | 4.7361 mL | |
| 10 mM | 0.2368 mL | 1.1840 mL | 2.3680 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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HTS Hit (VU0130734,4) to lead (VU0361591,5).Bioorg Med Chem Lett.2010 Sep 1;20(17):5175-8. |
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