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BioAssay: AID 631399

Drug uptake in rat striatum at 30 ug/kg, iv measured after 40 mins by LC/MS-MS analysis

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(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
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Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 631399
Data Source: ChEMBL (788847)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-24

Data Table ( Complete ):           View All Data
Tested Compound:
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: 102363
Target Type: TISSUE
Pref Name: Striatum
Organism: Rattus norvegicus
Tax ID: 10116
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
Assay Type: ADME

Assay Data Source: Scientific Literature

Assay Test Type: In vivo

BAO: Assay Format: organism-based format

Assay Tissue: Striatum

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1SUV activity commentSUV activity commentString
2SUV standard flagSUV standard flagInteger
3SUV qualifierSUV qualifierString
4SUV published valueSUV published valueFloat%
5SUV standard valueSUV standard valueFloat%

Data Table (Concise)
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