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BioAssay: AID 611383

Inhibition of human 5-lipoxygenase assessed as conjugated diene product formation using arachidonic acid by UV-vis spectrophotometer analysis

We report the discovery of novel small molecule inhibitors of platelet-type 12-human lipoxygenase, which display nanomolar activity against the purified enzyme, using a quantitative high-throughput screen (qHTS) on a library of 153607 compounds. These compounds also exhibit excellent specificity, >50-fold selectivity vs the paralogues, 5-human lipoxygenase, reticulocyte 15-human lipoxygenase more ..
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 Tested Compounds
 Tested Compounds
All(7)
 
 
Active(1)
 
 
Inconclusive(1)
 
 
Unspecified(5)
 
 
 Tested Substances
 Tested Substances
All(7)
 
 
Active(1)
 
 
Inconclusive(1)
 
 
Unspecified(5)
 
 
AID: 611383
Data Source: ChEMBL (761394)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-04-30
Modify Date: 2014-05-26

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Arachidonate 5-lipoxygenase; Short=5-LO; Short=5-lipoxygenase
Description ..   
Protein Family: Lipoxygenase
Comment ..   

Gene:ALOX5     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Discovery of potent and selective inhibitors of human platelet-type 12- lipoxygenase.

Abstract: We report the discovery of novel small molecule inhibitors of platelet-type 12-human lipoxygenase, which display nanomolar activity against the purified enzyme, using a quantitative high-throughput screen (qHTS) on a library of 153607 compounds. These compounds also exhibit excellent specificity, >50-fold selectivity vs the paralogues, 5-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity vs ovine cyclooxygenase-1 and human cyclooxygenase-2. Kinetic experiments indicate this chemotype is a noncompetitive inhibitor that does not reduce the active site iron. Moreover, chiral HPLC separation of two of the racemic lead molecules revealed a strong preference for the (-)-enantiomers (IC(50) of 0.43 # 0.04 and 0.38 # 0.05 muM) compared to the (+)-enantiomers (IC(50) of >25 muM for both), indicating a fine degree of selectivity in the active site due to chiral geometry. In addition, these compounds demonstrate efficacy in cellular models, which underscores their relevance to disease modification.
(PMID: 21739938)
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

Protein Target Class: enzyme reductase

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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