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BioAssay: AID 724032

Partial agonist activity at human 2:3 alpha4beta2 nAChR expressed in Xenopus laevis oocytes after 1 min by two electrode voltage clamp technique

In our search for selective agonists for the alpha(4)beta(2) subtype of the nicotinic acetylcholine receptors (nAChRs), we have synthesized and characterized a series of novel heterocyclic analogues of 3-(dimethylamino)butyl dimethylcarbamate (DMABC, 4). All new heterocyclic analogues, especially N,N-dimethyl-4-(1-methyl-1H-imidazol-2-yloxy)butan-2-amine (7), showed an improved binding more ..
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 Tested Compounds
 Tested Compounds
All(4)
 
 
Active(4)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Active(4)
 
 
 Related BioAssays
 Related BioAssays
AID: 724032
Data Source: ChEMBL (936598)
Depositor Category: Literature, Extracted
Deposit Date: 2013-11-07

Data Table ( Complete ):           Active    All
Targets
Sequence: RecName: Full=Neuronal acetylcholine receptor subunit beta-2; Flags: Precursor
Description ..   
Protein Family: Neurotransmitter-gated ion-channel ligand binding domain
Comment ..   

Gene:CHRNB2     Related Protein 3D Structures     More BioActivity Data..


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BioActive Compounds: 4
Description:
Title: Synthesis, pharmacology, and biostructural characterization of novel alpha4beta2 nicotinic acetylcholine receptor agonists.

Abstract: In our search for selective agonists for the alpha(4)beta(2) subtype of the nicotinic acetylcholine receptors (nAChRs), we have synthesized and characterized a series of novel heterocyclic analogues of 3-(dimethylamino)butyl dimethylcarbamate (DMABC, 4). All new heterocyclic analogues, especially N,N-dimethyl-4-(1-methyl-1H-imidazol-2-yloxy)butan-2-amine (7), showed an improved binding selectivity profile in favor of alpha(4)beta(2) over other nAChR subtypes, primarily due to impaired binding at beta(4) containing receptors. This observation can be rationalized based on cocrystal structures of (R)-4 and (R)-7 bound to acetylcholine binding protein from Lymnaea stagnalis. Functional characterization at both (alpha(4))(2)(beta(2))(3) and (alpha(4))(3)(beta(2))(2) receptors using two-electrode voltage clamp techniques in Xenopus laevis oocytes indicates that the investigated compounds interact differently with the two receptor stoichiometries. Compound 7 is an efficacious agonist at both alpha(4)-beta(2) and alpha(4)-alpha(4) binding sites, while the close analogue N,N-dimethyl-4-(1,4-dimethyl-1H-imidazol-2-yloxy)butan-2-amine (9) primarily activates via alpha(4)-beta(2) binding sites. The results suggest that it may be possible to rationally design compounds with specific stoichiometry preferences.
(PMID: 23256554)
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: 104283

ChEMBL Target Type: Target is a defined protein complex, consisting of multiple subunits

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
2EC50 activity commentEC50 activity commentString
3EC50 standard flagEC50 standard flagInteger
4EC50 qualifierEC50 qualifierString
5EC50 published valueEC50 published valueFloatμM
6EC50 standard valueEC50 standard valueFloatnM
7EC50 binding domainsEC50 binding domainsString
8pEC50 activity commentpEC50 activity commentString
9pEC50 standard flagpEC50 standard flagInteger
10pEC50 qualifierpEC50 qualifierString
11pEC50 published valuepEC50 published valueFloat
12pEC50 standard valuepEC50 standard valueFloat
13pEC50 binding domainspEC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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