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BioAssay: AID 751322

Inhibition of human recombinant GSK3alpha by FRET assay

Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases beta-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3alpha and beta, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds more ..
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 Tested Compounds
 Tested Compounds
All(23)
 
 
Active(23)
 
 
 Tested Substances
 Tested Substances
All(23)
 
 
Active(23)
 
 
AID: 751322
Data Source: ChEMBL (964510)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2014-05-03
Modify Date: 2014-08-23

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Glycogen synthase kinase-3 alpha; Short=GSK-3 alpha; AltName: Full=Serine/threonine-protein kinase GSK3A
Description ..   
Protein Family: The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3
Comment ..   

Gene:GSK3A     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 23
Description:
Title: Structure-based optimization of oxadiazole-based GSK-3 inhibitors.

Abstract: Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases beta-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3alpha and beta, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP-binding pocket [1]. Particularly, the oxadiazole scaffold provided potent and selective GSK-3 inhibitors. For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK-3alpha and 17 nM for GSK-3beta. In addition, the benzodioxane 8g showed up to 27-fold selectivity for GSK-3alpha over GSK-3beta, with an IC50 of 35 nM for GSK-3alpha. Two GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay to evaluate simultaneously permeability and safety.
(PMID: 22749643)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface 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 valueFloatμM
10IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

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