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BioAssay: AID 239589

Displacement of [3H]-cytisine from Alpha4-beta2 Nicotinic acetylcholine receptor of rat brain homogenates

The homology models of the extracellular domains of the neuronal alpha4beta2 (pdb code: 1ole) and ganglionic alpha3beta4 (pdb code: 1olf) rat nicotinic acetylcholine receptor (nAChR) subtypes were refined and energetically minimized. In this work, a series of nAChR ligands (1-15) were docked into the modeled binding cavity of both receptors. High-affinity, toxic ligands such as epibatidine (1) more ..
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 Tested Compounds
 Tested Compounds
All(15)
 
 
Active(14)
 
 
Inconclusive(1)
 
 
 Tested Substances
 Tested Substances
All(15)
 
 
Active(14)
 
 
Inconclusive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 239589
Data Source: ChEMBL (303683)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2013-11-18

Data Table ( Complete ):           Active    All
Targets
Sequence: RecName: Full=Neuronal acetylcholine receptor subunit beta-2; AltName: Full=Neuronal acetylcholine receptor non-alpha-1 chain; Short=N-alpha 1; 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: 14
Description:
Title: Ligand selectivity for the acetylcholine binding site of the rat alpha4beta2 and alpha3beta4 nicotinic subtypes investigated by molecular docking.

Abstract: The homology models of the extracellular domains of the neuronal alpha4beta2 (pdb code: 1ole) and ganglionic alpha3beta4 (pdb code: 1olf) rat nicotinic acetylcholine receptor (nAChR) subtypes were refined and energetically minimized. In this work, a series of nAChR ligands (1-15) were docked into the modeled binding cavity of both receptors. High-affinity, toxic ligands such as epibatidine (1) and dechloroepibatidine (2) docked into cluster 1 with the charged tertiary amino group, forming a pi-cation interaction with Trp 147 on the (+) side of the alpha4 subunit and establishing a characteristic H-bond with the Lys 77 on the (-) side of the beta2 subunit. The nontoxic ligands such as 33bMet (3), (S)-A-85380 (4), and acetylcholine (6) docked into cluster 2 with the same pi-cation interaction but with the rest of the molecule occupying a different moiety of the binding pocket. Molecular docking into the alpha3beta4 subtype showed that both enantiomers of 1 (1a and 1b) are representative templates for ligands with affinity toward this ganglionic nAChR subtype. The ranking scores of the docked molecules confirm the existence of structure-dependent subtype selectivity and shed light on the design of specific and selective alpha4beta2 nAChR subtype ligands.
(PMID: 16078832)
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: 104290

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

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6Ki activity commentKi activity commentString
7Ki standard flagKi standard flagInteger
8Ki qualifierKi qualifierString
9Ki published valueKi published valueFloatnM
10Ki standard valueKi standard valueFloatnM
11Ki binding domainsKi binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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