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BioAssay: AID 631359

Displacement of [3H]diprenorphine from human opioid kappa receptor expressed in CHO cells after 120 mins by scintillation counting

Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for kappa opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide (25) had a K(i) = 0.565 nM for kappa opioid receptor binding while having a more ..
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 Tested Compounds
 Tested Compounds
All(18)
 
 
Active(18)
 
 
 Tested Substances
 Tested Substances
All(18)
 
 
Active(18)
 
 
AID: 631359
Data Source: ChEMBL (788807)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-23

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Kappa-type opioid receptor; Short=K-OR-1; Short=KOR-1
Description ..   
Protein Family: Serpentine type 7TM GPCR chemoreceptor Srx
Comment ..   

Gene:OPRK1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 18
Description:
Title: Discovery of aminobenzyloxyarylamides as kappa opioid receptor selective antagonists: application to preclinical development of a kappa opioid receptor antagonist receptor occupancy tracer.

Abstract: Arylphenylpyrrolidinylmethylphenoxybenzamides were found to have high affinity and selectivity for kappa opioid receptors. On the basis of receptor binding assays in Chinese hamster ovary (CHO) cells expressing cloned human opioid receptors, (S)-3-fluoro-4-(4-((2-(3-fluorophenyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide (25) had a K(i) = 0.565 nM for kappa opioid receptor binding while having a K(i) = 35.8 nM for mu opioid receptors and a K(i) = 211 nM for delta opioid receptor binding. Compound 25 was also a potent antagonist of kappa opioid receptors when tested in vitro using a [(35)S]-guanosine 5'O-[3-thiotriphosphate] ([(35)S]GTP-gamma-S) functional assay in CHO cells expressing cloned human opioid receptors. Compounds were also evaluated for potential use as receptor occupancy tracers. Tracer evaluation was done in vivo, using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods, precluding the need for radiolabeling. (S)-3-Chloro-4-(4-((2-(pyridine-3-yl)pyrrolidin-1-yl)methyl)phenoxy)benzamide (18) was found to have favorable properties for a tracer for receptor occupancy, including good specific versus nonspecific binding and good brain uptake.
(PMID: 21958337)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

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
BAO: Assay Format: cell-based format
Assay Cell Type: CHO
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6Ki activity commentKi activity commentString
7Ki standard flagKi standard flagInteger
8Ki qualifierKi qualifierString
9Ki published valueKi published valueFloatnM
10Ki standard valueKi standard valueFloatnM
11Ki binding domainsKi binding domainsString

* Activity Concentration.

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