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BioAssay: AID 698555

Binding affinity to mGluR5 receptor in Wistar rat brain at 1 to 10 nM after 45 mins by autoradiography in presence of ABP688

In the search for an optimal fluorine-18-labeled positron emission tomography (PET) radiotracer for imaging metabotropic glutamate receptor subtype 5 (mGluR5), we have prepared a series of five alpha-fluorinated derivatives based on the ABP688 structural manifold by application of a two-step enolization/NFSI alpha-fluorination method. Their binding affinities were evaluated in vitro, and the most more ..
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 Tested Compounds
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Active(1)
 
 
 Tested Substances
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AID: 698555
Data Source: ChEMBL (859299)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2014-05-25

Data Table ( Complete ):           View Active Data    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..
BioActive Compound: 1
Description:
Title: Synthesis and evaluation of novel alpha-fluorinated (E)-3-((6-methylpyridin-2-yl)ethynyl)cyclohex-2-enone-O-methyl oxime (ABP688) derivatives as metabotropic glutamate receptor subtype 5 PET radiotracers.

Abstract: In the search for an optimal fluorine-18-labeled positron emission tomography (PET) radiotracer for imaging metabotropic glutamate receptor subtype 5 (mGluR5), we have prepared a series of five alpha-fluorinated derivatives based on the ABP688 structural manifold by application of a two-step enolization/NFSI alpha-fluorination method. Their binding affinities were evaluated in vitro, and the most promising candidate (Z)-16 exhibited a K(i) of 5.7 nM and a clogP value of 2.3. The synthesis of the precursor tosylate (E)-22 revealed a preference for the (E)-configurational isomer (K(i) = 31.2 nM), and successful radiosynthesis afforded (E)-[(18)F]-16 which was used as a model PET tracer to establish plasma and PBS stability. (E)-[(18)F]-16 (K(d) = 70 nM) exhibited excellent specificity for mGluR5 in autoradiographic studies on horizontal rat brain slices in vitro.
(PMID: 22822714)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

Target Type: Target is a single protein chain

Result Definitions
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

Data Table (Concise)
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Classification
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