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BioAssay: AID 730862

Agonist activity at FLAG-tagged mu-type opioid receptor (unknown origin) expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation after 30 mins by liquid scintillation counting analysis

Recently we reported the synthesis and structure-activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural alpha-methylene-beta-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt(1), (R/S)-betaPro(2), and (ph)Map(4)/(2-furyl)Map(4). All of the analogues showed a high affinity for the mu-opioid receptor (MOR) and increased stability more ..
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 Tested Compounds
 Tested Compounds
All(11)
 
 
Active(11)
 
 
 Tested Substances
 Tested Substances
All(11)
 
 
Active(11)
 
 
AID: 730862
Data Source: ChEMBL (943430)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-11-07
Modify Date: 2014-05-27

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 Compounds: 11
Description:
Title: Design, synthesis, and pharmacological characterization of novel endomorphin-1 analogues as extremely potent mu-opioid agonists.

Abstract: Recently we reported the synthesis and structure-activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural alpha-methylene-beta-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt(1), (R/S)-betaPro(2), and (ph)Map(4)/(2-furyl)Map(4). All of the analogues showed a high affinity for the mu-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt(1)-(R)-betaPro(2)-Trp(3)-(2-furyl)Map(4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (Ki(mu) = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, Emax = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier.
(PMID: 23477419)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Assay Cell Type: HEK293

Target Type: Target is a single protein chain

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 valueFloatnM
10EC50 standard valueEC50 standard valueFloatnM
11EC50 data validityEC50 data validityString
12EC50 binding domainsEC50 binding domainsString
13Inhibition activity commentInhibition activity commentString
14Inhibition standard flagInhibition standard flagInteger
15Inhibition qualifierInhibition qualifierString
16Inhibition published valueInhibition published valueFloat
17Inhibition standard valueInhibition standard valueFloat
18Inhibition data validityInhibition data validityString
19Inhibition binding domainsInhibition binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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