VU 0364439 1246086-78-1_GluR_Neuronal Signaling_Signaling Pathways_Products

VU 0364439 (VU0364439; VU-0364439) is a mGlu4 (metabotropic glutamate receptor 4) positive allosteric modulator (PAM) with important biological activity. It inhibits mGlu4 with an EC50 value of 19.8 nM. Due to the fact that VU 0364439 possessed less favorable pharmacokinetic properties, thus it can not be 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 Parkinson's disease, anxiety, and pain. mGlu4 PAMs may have several advantages over mGlu4 agonists for a number of reasons.

Physicochemical Properties

Molecular Formula

C18H13CL2N3O3S

Molecular Weight

422.29

Exact Mass

421.005

Elemental Analysis

C, 51.20; H, 3.10; Cl, 16.79; N, 9.95; O, 11.37; S, 7.59

CAS #

1246086-78-1

Related CAS #

1246086-78-1

PubChem CID

46934289

Appearance

White to off-white solid powder

Density

1.5±0.1 g/cm3

Index of Refraction

1.686

LogP

3.82

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

614

Defined Atom Stereocenter Count

SMILES

O=C(C1=NC=CC=C1)NC2=CC=C(S(=O)(NC3=CC=CC=C3Cl)=O)C(Cl)=C2

InChi Key

IXHCGJXBIHHIEF-UHFFFAOYSA-N

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)

Chemical Name

N-[3-chloro-4-[(2-chlorophenyl)sulfamoyl]phenyl]pyridine-2-carboxamide

Synonyms

VU0364439, VU-0364439, VU 0364439

HS Tariff Code

2934.99.9001

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)

Biological Activity

ln Vitro

In vitro activity: 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

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).

Animal Protocol

N/A

References

Bioorg Med Chem Lett.2010 Sep 1;20(17):5175-8;J Med Chem.2011 Jul 28;54(14):5070-81.

Solubility Data

Solubility (In Vitro)

DMSO: 85 mg/mL (201.3 mM)

Water:<1 mg/mL

Ethanol:<1 mg/mL

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.

PeptideDB

VU 0364439 1246086-78-1

CAS No.: 1246086-78-1

Physicochemical Properties

Biological Activity

Solubility Data