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BioAssay: AID 683164

Ratio of MPEP Ki to compound Ki for mGluR5 in Sprague-Dawley rat brain membrane

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(2)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Unspecified(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 683164
Data Source: ChEMBL (840311)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-08-26

Data Table ( Complete ):           View All Data
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..
Tested Compounds:
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)
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ratio Ki activity commentRatio Ki activity commentString
2Ratio Ki standard flagRatio Ki standard flagInteger
3Ratio Ki qualifierRatio Ki qualifierString
4Ratio Ki published valueRatio Ki published valueFloat
5Ratio Ki standard valueRatio Ki standard valueFloat

Data Table (Concise)
Data Table ( Complete ):     View All Data
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