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BioAssay: AID 779520

Binding affinity to wild type MOR (unknown origin) expressed in CHO cells after 15 mins by Ca2+ mobilization assay

Highly selective opioid receptor antagonists are essential pharmacological probes in opioid receptor structural characterization and opioid agonist functional studies. Currently, there is no highly selective, nonpeptidyl and reversible mu opioid receptor antagonist available. Among a series of naltrexamine derivatives that have been designed and synthesized, two compounds, NAP and NAQ, were more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Active(3)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Active(3)
 
 
AID: 779520
Data Source: ChEMBL (989553)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2014-05-03
Modify Date: 2014-08-25

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: 3
Description:
Title: Binding mode characterization of 6alpha- and 6beta-N-heterocyclic substituted naltrexamine derivatives via docking in opioid receptor crystal structures and site-directed mutagenesis studies: application of the 'message-address' concept in development of mu opioid receptor selective antagonists.

Abstract: Highly selective opioid receptor antagonists are essential pharmacological probes in opioid receptor structural characterization and opioid agonist functional studies. Currently, there is no highly selective, nonpeptidyl and reversible mu opioid receptor antagonist available. Among a series of naltrexamine derivatives that have been designed and synthesized, two compounds, NAP and NAQ, were previously identified as novel leads for this purpose based on their in vitro and in vivo pharmacological profiles. Both compounds displayed high binding affinity and selectivity to the mu opioid receptor. To further study the interaction of these two ligands with the three opioid receptors, the recently released opioid receptor crystal structures were employed in docking studies to further test our original hypothesis that the ligands recognize a unique 'address' domain in the mu opioid receptor involving Trp318 that facilitates their selectivity. These modeling results were supported by site-directed mutagenesis studies on the mu opioid receptor, where the mutants Y210A and W318A confirmed the role of the latter in binding. Such work not only enriched the 'message-address' concept, also facilitated our next generation ligand design and development.
(PMID: 24055076)
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: CHO
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatnM
6IC50 standard valueIC50 standard valueFloatnM
7IC50 Binding Efficiency Index(nM)IC50 Binding Efficiency Index(nM)Float
8IC50 Surface Efficiency Index(nM)IC50 Surface Efficiency Index(nM)Float
9IC50 Ligand EfficiencyIC50 Ligand EfficiencyFloat
10IC50 Lipophilic Ligand EfficiencyIC50 Lipophilic Ligand EfficiencyFloat
11Ki activity commentKi activity commentString
12Ki standard flagKi standard flagInteger
13Ki qualifierKi qualifierString
14Ki published valueKi published valueFloatnM
15Ki standard valueKi standard valueFloatnM
16Ki Binding Efficiency Index(nM)Ki Binding Efficiency Index(nM)Float
17Ki Surface Efficiency Index(nM)Ki Surface Efficiency Index(nM)Float
18Ki Ligand EfficiencyKi Ligand EfficiencyFloat
19Ki Lipophilic Ligand EfficiencyKi Lipophilic Ligand EfficiencyFloat

* Activity Concentration.

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