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BioAssay: AID 551524

Inhibition of rat liver cytosolic TrxR1 at 50 to 100 uM by spectrophotometry in presence of 0.025 mM NADPH

Cytosolic (TrxR1) and mitochondrial (TrxR2) thioredoxin reductases experience pronounced concentration- and time-dependent inhibition when incubated with the two naphthodianthrones hypericin and pseudohypericin. Pseudohypericin turned out to be a quite strong inhibitor of TrxR1 (IC(50)=4.40muM) being far more effective than hypericin (IC(50)=157.08muM). In turn, the IC(50) values measured toward more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Active(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Active(1)
 
 
AID: 551524
Data Source: ChEMBL (700052)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-09-18
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Thioredoxin reductase 1, cytoplasmic; Short=TR; AltName: Full=NADPH-dependent thioredoxin reductase; AltName: Full=Thioredoxin reductase TR1
Description ..   
Protein Family: Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
Comment ..   

Gene:TXNRD1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: Hypericins and thioredoxin reductase: Biochemical and docking studies disclose the molecular basis for effective inhibition by naphthodianthrones.

Abstract: Cytosolic (TrxR1) and mitochondrial (TrxR2) thioredoxin reductases experience pronounced concentration- and time-dependent inhibition when incubated with the two naphthodianthrones hypericin and pseudohypericin. Pseudohypericin turned out to be a quite strong inhibitor of TrxR1 (IC(50)=4.40muM) being far more effective than hypericin (IC(50)=157.08muM). In turn, the IC(50) values measured toward TrxR2 were 7.45muM for pseudohypericin and 43.12muM for hypericin. When compared to pseudohypericin, the inhibition caused by hypericin usually required significantly longer times, in particular on TrxR1. These important differences in the inhibitory potencies and profiles were analysed through a molecular modeling approach. Notably, both compounds were found to accommodate in the NADPH-binding pocket of the enzyme. The binding of the two naphthodianthrones to thioredoxin reductase seems to be particularly strong as the inhibitory effects were fully retained after gel filtration. Also, we found that TrxR inhibition by hypericin and pseudohypericin does not involve the active site selenol/thiol motif as confirmed by biochemical and modeling studies. The resulting inhibition pattern is very similar to that produced by the two naphthodianthrones on glutathione reductase. As the thioredoxin system is highly overexpressed in cancer cells, its inhibition by hypericin and pseudohypericin, natural compounds showing appreciable anticancer properties, might offer new clues on their mechanism of action and open interesting perspectives for future tumor therapies.
(PMID: 21106380)
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
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Inhibition activity commentInhibition activity commentString
2Inhibition standard flagInhibition standard flagInteger
3Inhibition qualifierInhibition qualifierString
4Inhibition published valueInhibition published valueFloat
5Inhibition standard valueInhibition standard valueFloat

Data Table (Concise)
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