Bookmark and Share
BioAssay: AID 779593

Agonist activity at human mu opioid receptor expressed in HEK293 cells assessed as beta-arrestin recruitment by chemiluminescence assay relative to morphine

The concept of "ligand bias" at G protein coupled receptors has been introduced to describe ligands which preferentially stimulate one intracellular signaling pathway over another. There is growing interest in developing biased G protein coupled receptor ligands to yield safer, better tolerated, and more efficacious drugs. The classical mu opioid morphine elicited increased efficacy and more ..
_
   
 Tested Compounds
 Tested Compounds
All(35)
 
 
Inconclusive(14)
 
 
Unspecified(21)
 
 
 Tested Substances
 Tested Substances
All(35)
 
 
Inconclusive(14)
 
 
Unspecified(21)
 
 
 Related BioAssays
 Related BioAssays
AID: 779593
Data Source: ChEMBL (989753)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2014-05-03
Modify Date: 2014-12-06

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Mu-type opioid receptor; Short=M-OR-1; Short=MOR-1; AltName: Full=Mu opiate receptor; AltName: Full=Mu opioid receptor; Short=MOP; Short=hMOP
Description ..   
Protein Family: Olfactory receptor
Comment ..   

Gene:OPRM1     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Structure-activity relationships and discovery of a G protein biased mu opioid receptor ligand, [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the treatment of acute severe pain.

Abstract: The concept of "ligand bias" at G protein coupled receptors has been introduced to describe ligands which preferentially stimulate one intracellular signaling pathway over another. There is growing interest in developing biased G protein coupled receptor ligands to yield safer, better tolerated, and more efficacious drugs. The classical mu opioid morphine elicited increased efficacy and duration of analgesic response with reduced side effects in beta-arrestin-2 knockout mice compared to wild-type mice, suggesting that G protein biased mu opioid receptor agonists would be more efficacious with reduced adverse events. Here we describe our efforts to identify a potent, selective, and G protein biased mu opioid receptor agonist, TRV130 ((R)-30). This novel molecule demonstrated an improved therapeutic index (analgesia vs adverse effects) in rodent models and characteristics appropriate for clinical development. It is currently being evaluated in human clinical trials for the treatment of acute severe pain.
(PMID: 24063433)
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: HEK293
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Efficacy activity commentEfficacy activity commentString
2Efficacy standard flagEfficacy standard flagInteger
3Efficacy qualifierEfficacy qualifierString
4Efficacy published valueEfficacy published valueFloat%
5Efficacy standard valueEfficacy standard valueFloat%

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