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BioAssay: AID 631392

Agonist activity at human opioid kappa receptor expressed in CHO cells assessed as stimulation of [35S]-GTPgammaS binding at 10 uM

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)
 
 
Inactive(18)
 
 
 Tested Substances
 Tested Substances
All(18)
 
 
Inactive(18)
 
 
 Related BioAssays
 Related BioAssays
AID: 631392
Data Source: ChEMBL (788840)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2013-11-17

Data Table ( Complete ):           All
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..
Tested Compounds:
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)
Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Assay Cell Type: CHO

ChEMBL Target ID: 137

ChEMBL 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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