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BioAssay: AID 725947

Inhibition of recombinant firefly luciferase after 20 mins by luminescence assay

Luciferase reporter assays are commonly used in high-throughput screening methods. Here, we report new firefly luciferase (FLuc) inhibitors based on 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles, which showed up as "false positives" in a luciferase reporter gene-based assay for nuclear receptor antagonists. The inhibition was shown to be noncompetitive more ..
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 Tested Compounds
 Tested Compounds
All(65)
 
 
Active(60)
 
 
Inconclusive(5)
 
 
 Tested Substances
 Tested Substances
All(65)
 
 
Active(60)
 
 
Inconclusive(5)
 
 
AID: 725947
Data Source: ChEMBL (938513)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-11-07
Modify Date: 2014-08-27

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 Compounds: 60
Description:
Title: Discovery of 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles as potent firefly luciferase inhibitors.

Abstract: Luciferase reporter assays are commonly used in high-throughput screening methods. Here, we report new firefly luciferase (FLuc) inhibitors based on 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles, which showed up as "false positives" in a luciferase reporter gene-based assay for nuclear receptor antagonists. The inhibition was shown to be noncompetitive for both natural enzyme substrates (d-luciferin and ATP) and selective to FLuc and proven to arise from a direct interaction between the enzyme and the inhibitor. Of the 63 evaluated compounds, 28 showed significantly better inhibition potency than the well-known inhibitor resveratrol (IC(50) = 59 nM), with five compounds having distinctly subnanomolar IC(50) values. The most efficient compounds inhibited the luminescence at concentrations lower than (1)/(100) in comparison to resveratrol (lowest IC(50) = 0.26 nM) and can thus be considered to belong to the most potent FLuc inhibitors reported thus far. Overall, the novel inhibitors form a unique molecular library for structure-activity relationship (SAR) analyses.
(PMID: 23286196)
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 valueFloat
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)
Data Table ( Complete ):     View Active Data    View All Data
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