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BioAssay: AID 779596

Agonist activity at human mu opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation by fluorescence assay

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 ..
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 Tested Compounds
 Tested Compounds
All(36)
 
 
Active(36)
 
 
 Tested Substances
 Tested Substances
All(36)
 
 
Active(36)
 
 
AID: 779596
Data Source: ChEMBL (989756)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2014-05-03
Modify Date: 2014-12-06

Data Table ( Complete ):           View Active Data    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..
BioActive Compounds: 36
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)
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: HEK293
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6EC50 activity commentEC50 activity commentString
7EC50 standard flagEC50 standard flagInteger
8EC50 qualifierEC50 qualifierString
9EC50 published valueEC50 published valueFloat
10EC50 standard valueEC50 standard valueFloatnM
11EC50 activity commentEC50 activity commentString
12EC50 standard flagEC50 standard flagInteger
13EC50 qualifierEC50 qualifierString
14EC50 published valueEC50 published valueFloatnM
15EC50 standard valueEC50 standard valueFloatnM

* Activity Concentration.

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