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BioAssay: AID 739880

Antagonist activity at human mu opioid receptor expressed in CHO cell membrane assessed as inhibition of DAMGO-induced [35S]GTPgammaS binding after 60 mins by liquid scintillation counting

Derivatives of the lead compound N-BPE-8-CAC (1) where each CH of the biphenyl group was individually replaced by N were prepared in hopes of identifying high affinity ligands with improved aqueous solubility. Compared to 1, binding affinities of the five possible pyridinyl derivatives for the mu opioid receptor were between threefold lower to fivefold higher with the Ki of the most potent more ..
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 Tested Compounds
 Tested Compounds
All(2)
 
 
Active(1)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(2)
 
 
Active(1)
 
 
Inactive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 739880
Data Source: ChEMBL (952448)
Depositor Category: Literature, Extracted
Deposit Date: 2013-11-07

Data Table ( Complete ):           Active    All
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: Serpentine type 7TM GPCR chemoreceptor Srx
Comment ..   

Gene:OPRM1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. Part 9: Synthesis, characterization and molecular modeling of pyridinyl isosteres of N-BPE-8-CAC (1), a high affinity ligand for opioid receptors.

Abstract: Derivatives of the lead compound N-BPE-8-CAC (1) where each CH of the biphenyl group was individually replaced by N were prepared in hopes of identifying high affinity ligands with improved aqueous solubility. Compared to 1, binding affinities of the five possible pyridinyl derivatives for the mu opioid receptor were between threefold lower to fivefold higher with the Ki of the most potent compound being 0.064 nM. Docking of 8-CAC (2) into the unliganded binding site of the mouse mu opioid receptor (pdb: 4DKL) revealed that 8-CAC and beta-FNA (from 4DKL) make nearly identical interactions with the receptor. However, for 1 and the new pyridinyl derivatives 4-8, binding is not tolerated in the 8-CAC binding mode due to the steric constraints of the large N-substituents. Either an alternative binding mode or rearrangement of the protein to accommodate these modifications may account for their high binding affinity.
(PMID: 23434225)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 129

ChEMBL Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatnM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 binding domainsIC50 binding domainsString
12Inhibition activity commentInhibition activity commentString
13Inhibition standard flagInhibition standard flagInteger
14Inhibition qualifierInhibition qualifierString
15Inhibition published valueInhibition published valueFloat
16Inhibition standard valueInhibition standard valueFloat
17Inhibition binding domainsInhibition binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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