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BioAssay: AID 684908

Agonist activity at rat alpha7 nAChR expressed in GH4C1 cells assessed as calcium influx measured every 1 sec for 1 min followed by every 30 secs for 10 mins by FLIPR assay

Alpha-7 nicotinic acetylcholine receptors (alpha7 nAChR) are implicated in the modulation of many cognitive functions such as attention, working memory, and episodic memory. For this reason, alpha7 nAChR agonists represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort, around our more ..
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 Tested Compounds
 Tested Compounds
All(30)
 
 
Active(25)
 
 
Inactive(3)
 
 
Unspecified(2)
 
 
 Tested Substances
 Tested Substances
All(30)
 
 
Active(25)
 
 
Inactive(3)
 
 
Unspecified(2)
 
 
AID: 684908
Data Source: ChEMBL (842055)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-05-16
Modify Date: 2014-05-27

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Neuronal acetylcholine receptor subunit alpha-7; Flags: Precursor
Description ..   
Protein Family: Neurotransmitter-gated ion-channel ligand binding domain
Comment ..   

Gene:CHRNA7     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 25
Description:
Title: Discovery of a novel alpha-7 nicotinic acetylcholine receptor agonist series and characterization of the potent, selective, and orally efficacious agonist 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (SEN15924, WAY-361789).

Abstract: Alpha-7 nicotinic acetylcholine receptors (alpha7 nAChR) are implicated in the modulation of many cognitive functions such as attention, working memory, and episodic memory. For this reason, alpha7 nAChR agonists represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort, around our previously reported chemical series, permitted the discovery of a novel class of alpha7 nAChR agonists with improved selectivity, in particular against the alpha3 receptor subtype and better ADME profile. The exploration of this series led to the identification of 5-(4-acetyl[1,4]diazepan-1-yl)pentanoic acid [5-(4-methoxyphenyl)-1H-pyrazol-3-yl] amide (25, SEN15924, WAY-361789), a novel, full agonist of the alpha7 nAChR that was evaluated in vitro and in vivo. Compound 25 proved to be potent and selective, and it demonstrated a fair pharmacokinetic profile accompanied by efficacy in rodent behavioral cognition models (novel object recognition and auditory sensory gating).
(PMID: 22468936)
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: Functional

Assay Data Source: Scientific Literature

Assay Test Type: In vitro

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
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

* Activity Concentration.

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