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BioAssay: AID 707503

Inhibition of human recombinant GSK3alpha expressed in insect cells using YRRAAVPPSPSLSRHSSPHQ-phosphoS-EDEEE as substrate and [gamma33P]ATP after 30 mins by scintillation counting

DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases) are implicated in the onset and development of Alzheimer's disease and Down syndrome. The marine sponge alkaloid leucettamine B was recently identified as an inhibitor of DYRKs/CLKs. Synthesis of analogues (leucettines) led to an optimized product, leucettine L41. Leucettines were cocrystallized with more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Active(2)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Active(2)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 707503
Data Source: ChEMBL (875246)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2013-11-18

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 Compounds: 2
Description:
Title: Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B.

Abstract: DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases) are implicated in the onset and development of Alzheimer's disease and Down syndrome. The marine sponge alkaloid leucettamine B was recently identified as an inhibitor of DYRKs/CLKs. Synthesis of analogues (leucettines) led to an optimized product, leucettine L41. Leucettines were cocrystallized with DYRK1A, DYRK2, CLK3, PIM1, and GSK-3beta. The selectivity of L41 was studied by activity and interaction assays of recombinant kinases and affinity chromatography and competition affinity assays. These approaches revealed unexpected potential secondary targets such as CK2, SLK, and the lipid kinase PIKfyve/Vac14/Fig4. L41 displayed neuroprotective effects on glutamate-induced HT22 cell death. L41 also reduced amyloid precursor protein-induced cell death in cultured rat brain slices. The unusual multitarget selectivity of leucettines may account for their neuroprotective effects. This family of kinase inhibitors deserves further optimization as potential therapeutics against neurodegenerative diseases such as Alzheimer's disease.
(PMID: 22998443)
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

* Activity Concentration.

Data Table (Concise)
Classification
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