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BioAssay: AID 683165

Inverse agonist activity at rat mGluR5 expressed in HEK293A cells coexpressing Gqalpha assessed as inhibition of quisqualic-induced D-myo-inositol 1 production by ELISA

Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGluR5) have shown promising results in preclinical models for anxiety and drug abuse. Here we describe a series of aryl-substituted alkynyl analogues of the prototypic mGluR5 NAM 2-methyl-6-(phenylethynyl)pyridine (MPEP, 1). Displacement of [(3)H]1 binding in rat brain membranes showed that several of these novel more ..
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 Tested Compounds
 Tested Compounds
All(19)
 
 
Active(19)
 
 
 Tested Substances
 Tested Substances
All(19)
 
 
Active(19)
 
 
AID: 683165
Data Source: ChEMBL (840312)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-05-27

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Metabotropic glutamate receptor 5; Short=mGluR5; Flags: Precursor
Description ..   
Protein Family: Ligand binding domain of the group I metabotropic glutamate receptor
Comment ..   

Gene:GRM5     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 19
Description:
Title: Metabotropic glutamate receptor 5 negative allosteric modulators as novel tools for in vivo investigation.

Abstract: Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGluR5) have shown promising results in preclinical models for anxiety and drug abuse. Here we describe a series of aryl-substituted alkynyl analogues of the prototypic mGluR5 NAM 2-methyl-6-(phenylethynyl)pyridine (MPEP, 1). Displacement of [(3)H]1 binding in rat brain membranes showed that several of these novel compounds displayed high affinity binding (K(i) < 10 nM) for mGluR5, with up to a 24-fold increase in affinity over 1. Replacements of the 2-position Me on the pyridyl ring of 1 along with various 3'-CN, 5'-substitutions were generally well tolerated. All of the active analogues in this series had cLogP values in the 2-5 range and displayed inverse agonist characteristics in an ELISA-based assay of G(q)alpha-mediated IP3 production. Compounds 7i and 7j produced in vivo effects in mouse models of anxiety-like behaviors more potently than 1 or 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP, 2), supporting their utility as in vivo tools.
(PMID: 22924094)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

Assay Test Type: In vitro

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatnM
6IC50 standard valueIC50 standard valueFloatnM
7Inhibition activity commentInhibition activity commentString
8Inhibition standard flagInhibition standard flagInteger
9Inhibition qualifierInhibition qualifierString
10Inhibition published valueInhibition published valueFloat
11Inhibition standard valueInhibition standard valueFloat

* Activity Concentration.

Data Table (Concise)
Classification
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