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BioAssay: AID 632387

Positive allosteric modulator activity at rat mGlu5 receptor at 10 uM by calcium mobilization assay relative to glutamate

There is an increasing amount of literature data showing the positive effects on preclinical antiparkinsonian rodent models with selective positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)). However, most of the data generated utilize compounds that have not been optimized for druglike properties, and as a consequence, they exhibit poor pharmacokinetic properties and more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Inactive(1)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Inactive(1)
 
 
Unspecified(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 632387
Data Source: ChEMBL (789835)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-23

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: Discovery, synthesis, and structure-activity relationship development of a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): characterization of a novel positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu(4)) with oral efficacy in an antiparkinsonian animal model.

Abstract: There is an increasing amount of literature data showing the positive effects on preclinical antiparkinsonian rodent models with selective positive allosteric modulators of metabotropic glutamate receptor 4 (mGlu(4)). However, most of the data generated utilize compounds that have not been optimized for druglike properties, and as a consequence, they exhibit poor pharmacokinetic properties and thus do not cross the blood-brain barrier. Herein, we report on a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides with improved PK properties with excellent potency and selectivity as well as improved brain exposure in rodents. Finally, ML182 was shown to be orally active in the haloperidol induced catalepsy model, a well-established antiparkinsonian model.
(PMID: 21966889)
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
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat
6FC activity commentFC activity commentString
7FC standard flagFC standard flagInteger
8FC qualifierFC qualifierString
9FC published valueFC published valueFloat
10FC standard valueFC standard valueFloat

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