VU 0364770


Catalog No. size PriceQuantity
M6574-2 2mg solid $101
M6574-10 10mg solid $391

Description

Cas:61350-00-3

Product Information:

VU0364770 is a Positive allosteric modulator at mGlu4 receptors (EC50 = 290 nM in mGlu4-expressing HEK 293 cells). VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease.

 

Chemical Formula: C12H9ClN2O

 

Exact Mass: 232.0403

 

Molecular Weight: 232.667

 

Elemental Analysis: C, 61.95; H, 3.90; Cl, 15.24; N, 12.04; O, 6.88

 

Synonym:

 

VU0364770

VU 0364770

VU 0364770

 

Chemical Name:

N-(3-Chlorophenyl)-2-pyridinecarboxamide

 

InChi Key:

SUYUTNCKIOLMAJ-UHFFFAOYSA-N

 

InChi Code: InChI=1S/C12H9ClN2O/c13-9-4-3-5-10(8-9)15-12(16)11-6-1-2-7-14-11/h1-8H,(H,15,16)

 

Smiles Code:

O=C(C1=NC=CC=C1)NC2=CC=CC(Cl)=C2

Technical Data:

 

Appearance: White to off-white crystalline solid

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

 

In Vitro

VU0364770 is a selective positive allosteric modulator of mGlu4 in recombinant systems. VU0364770 is a potent PAM of multiple signaling pathways that enhances the response of the rat and human mGlu4 receptors to the endogenous agonist glutamate. VU0364770 produces a concentration-dependent potentiation of the response to an EC20 concentration of glutamate with EC50 of 1.1±0.2 μM and increases the maximal response to glutamate from 100 to 227±17%. Because of concerns that this chemical scaffold might possess activity at MAO, full IC50 determinations is performed for VU0364770 at the MAO-A and MAO-B isoforms; these studies result in Kis of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively. When tested at a 10 μM concentration at each mGlu receptor, VU0364770 exhibits weak PAM activity (4.3-fold left shift of the glutamate CRC) at mGlu6 and antagonist activity (3.3-fold right shift of the glutamate CRC) at mGlu5 (compare to the 16.5-fold left shift of the glutamate concentration-response for mGlu4 at 10 μM). When further evaluated in a full concentration-response curve format, VU0364770 exhibits antagonist activity at mGlu5 with a potency of 17.9±5.5 μM and PAM activity at mGlu6 with a potency of 6.8±1.7 μM (compare with the potency of VU0364770 on the rat mGlu4 receptor of 290±80 nM).

 

In Vivo

VU0364770 exhibits suitable pharmacokinetic properties for systemic dosing in animal models. After intravenous administration, VU0364770 is rapidly clears from the systemic circulation (165 ml/min/kg) and exhibits a volume of distribution of 2.92 L/kg. VU0364770 is a highly protein-bound ligand displaying free fractions of 2.7 and 1.8% in human and rat plasma, respectively. VU0364770 also shows an improved pharmacokinetic profile relative to previously reported mGlu4 PAMs with enhanced central penetration and a total brain-to-plasma ratio of more than 1 after systemic administration of a 10 mg/kg dose. VU0364770 produces a dose-dependent reversal of haloperidol-induced catalepsy. VU0364770 dose-dependently reverses haloperidol (0.75 mg/kg)-induced catalepsy in rats, significant at doses of 10 to 56.6 mg/kg, after subcutaneous dosing (F6,69=8.04; p<0.001).

 

 

References

 

  1. Jones CK, Bubser M, Thompson AD, Dickerson JW, Turle-Lorenzo N, Amalric M, Blobaum AL, Bridges TM, Morrison RD, Jadhav S, Engers DW, Italiano K, Bode J, Daniels JS, Lindsley CW, Hopkins CR, Conn PJ, Niswender CM. The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease. J Pharmacol Exp Ther. 2012 Feb;340(2):404-21. doi: 10.1124/jpet.111.187443. PubMed PMID: 22088953; PubMed Central PMCID: PMC3263969.

 

  1. Iderberg H, Maslava N, Thompson AD, Bubser M, Niswender CM, Hopkins CR, Lindsley CW, Conn PJ, Jones CK, Cenci MA. Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia: Comparison between a positive allosteric modulator and an orthosteric agonist. Neuropharmacology. 2015 Aug;95:121-9. doi: 10.1016/j.neuropharm.2015.02.023. PubMed PMID: 25749357; PubMed Central PMCID: PMC4466038.

 

Products are for research use only. Not for human use.

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