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BioAssay: AID 722958

Inhibition of human recombinant GSK-3alpha using GS2 peptide as substrate and [gamma33P]-ATP after 12 mins by scintillation counting

Glycogen synthase kinase 3beta (GSK-3beta) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer's disease, mood disorders, diabetes and cancer. Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitors as new promising drugs for the treatment of these pathologies. We more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 722958
Data Source: ChEMBL (935524)
Depositor Category: Literature, Extracted
Deposit Date: 2013-11-07

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

Gene:GSK3A     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Evidence for a new binding mode to GSK-3: allosteric regulation by the marine compound palinurin.

Abstract: Glycogen synthase kinase 3beta (GSK-3beta) is widely recognised as a relevant player in the pathogenesis of several highly prevalent disorders such as Alzheimer's disease, mood disorders, diabetes and cancer. Therefore, this enzyme constitutes a highly attractive therapeutic target for the development of selective inhibitors as new promising drugs for the treatment of these pathologies. We describe here the isolation and biochemical characterization of the marine natural sesquiterpene palinurin as a GSK-3beta inhibitor. Experimental studies performed for characterizing the inhibitory mechanism indicate that GSK-3beta inhibition by palinurin cannot be competed out by ATP nor peptide substrate. Molecular modelling techniques have enabled us to propose an unconventional binding mode to GSK-3beta. Moreover, molecular dynamics simulations have identified an allosteric mechanism by which binding of palinurin leads to GSK-3beta inhibition. The inhibitory activities determined for a series of structurally related analogues support the proposed binding mode of palinurin, which is the first compound described to target this allosteric site. The results offer new opportunities for designing and developing selective inhibitors with novel mechanisms of action.
(PMID: 23354070)
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: 11017

ChEMBL Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface 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
11IC50 binding domainsIC50 binding domainsString
12pIC50 activity commentpIC50 activity commentString
13pIC50 standard flagpIC50 standard flagInteger
14pIC50 qualifierpIC50 qualifierString
15pIC50 published valuepIC50 published valueFloat
16pIC50 standard valuepIC50 standard valueFloat
17pIC50 binding domainspIC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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