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BioAssay: AID 438771

Inhibition of human recombinant GR after 15 mins in presence of NADPH

Schistosomiasis is a chronic parasitic disease affecting hundreds of millions of individuals worldwide. Current treatment depends on a single agent, praziquantel, raising concerns of emergence of resistant parasites. Here, we continue our explorations of an oxadiazole-2-oxide class of compounds we recently identified as inhibitors of thioredoxin glutathione reductase (TGR), a more ..
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 Tested Compounds
 Tested Compounds
All(22)
 
 
Active(3)
 
 
Unspecified(19)
 
 
 Tested Substances
 Tested Substances
All(22)
 
 
Active(3)
 
 
Unspecified(19)
 
 
 Related BioAssays
 Related BioAssays
AID: 438771
Data Source: ChEMBL (589949)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-08
Modify Date: 2013-11-16

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Glutathione reductase, mitochondrial; Short=GR; Short=GRase; Flags: Precursor
Description ..   
Protein Family: Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
Comment ..   

Gene:GSR     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 3
Description:
Title: Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis.

Abstract: Schistosomiasis is a chronic parasitic disease affecting hundreds of millions of individuals worldwide. Current treatment depends on a single agent, praziquantel, raising concerns of emergence of resistant parasites. Here, we continue our explorations of an oxadiazole-2-oxide class of compounds we recently identified as inhibitors of thioredoxin glutathione reductase (TGR), a selenocysteine-containing flavoenzyme required by the parasite to maintain proper cellular redox balance. Through systematic evaluation of the core molecular structure of this chemotype, we define the essential pharmacophore, establish a link between the nitric oxide donation and TGR inhibition, determine the selectivity for this chemotype versus related reductase enzymes, and present evidence that these agents can be modified to possess appropriate drug metabolism and pharmacokinetic properties. The mechanistic link between exogenous NO donation and parasite injury is expanded and better defined. The results of these studies verify the utility of oxadiazole-2-oxides as novel inhibitors of TGR and as efficacious antischistosomal agents.
(PMID: 19761212)
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: 12642

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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