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BioAssay: AID 366889

Inhibition of Photinus pyralis luciferase assessed as maximum inhibitory potency by quantitative high throughput screening

We measured the "druggability" of the ATP-dependent luciferase derived from the firefly Photuris pennsylvanica that was optimized using directed evolution (Ultra-Glo, Promega). Quantitative high-throughput screening (qHTS) was used to determine IC(50)s of 198899 samples against a formulation of Ultra-Glo luciferase (Kinase-Glo). We found that only 0.1% of the Kinase-Glo inhibitors more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
AID: 366889
Data Source: ChEMBL (514918)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2014-05-27

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Luciferin 4-monooxygenase; Short=Luciferase
Description ..   
Protein Family: Firefly luciferase of light emitting insects and 4-Coumarate-CoA Ligase (4CL)
Comment ..   

Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: A basis for reduced chemical library inhibition of firefly luciferase obtained from directed evolution.

Abstract: We measured the "druggability" of the ATP-dependent luciferase derived from the firefly Photuris pennsylvanica that was optimized using directed evolution (Ultra-Glo, Promega). Quantitative high-throughput screening (qHTS) was used to determine IC(50)s of 198899 samples against a formulation of Ultra-Glo luciferase (Kinase-Glo). We found that only 0.1% of the Kinase-Glo inhibitors showed an IC(50) < 10 microM compared to 0.9% found from a previous qHTS against the firefly luciferase from Photinus pyralis (lucPpy). Further, the maximum affinity identified in the lucPpy qHTS was 50 nM, while for Kinase-Glo this value increased to 600 nM. Compounds with interactions stretching outside the luciferin binding pocket were largely lost with Ultra-Glo luciferase. Therefore, Ultra-Glo luciferase will show less compound interference when used as an ATP sensor compared to lucPpy. This study demonstrates the power of large-scale quantitative analysis of structure-activity relationships (>100K compounds) in addressing important questions such as a target's druggability.
(PMID: 19215089)
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: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloatnM
5Activity standard valueActivity standard valueFloatnM

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