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BioAssay: AID 631363

Selectivity ratio of Ki for human opioid delta receptor expressed in HEK293 cells to Ki for human opioid kappa receptor expressed in CHO cells

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)
 
 
Unspecified(18)
 
 
 Tested Substances
 Tested Substances
All(18)
 
 
Unspecified(18)
 
 
 Related BioAssays
 Related BioAssays
AID: 631363
Data Source: ChEMBL (788811)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-24

Data Table ( Complete ):           View All 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)
Comment
Putative Target:
ChEMBL Target ID: 22226
Target Type: UNCHECKED
Pref Name: Unchecked
Confidence: Default value - Target unknown or has yet to be assigned
Relationship Type: Default value - Target has yet to be curated
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Binding
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Cell Type: HEK293
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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