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BioAssay: AID 393178

Effect on human HSPA1A ATPase activity assessed as fold change in Kcat at 100 uM relative to control

Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite more ..
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 Tested Compounds
 Tested Compounds
All(9)
 
 
Unspecified(9)
 
 
 Tested Substances
 Tested Substances
All(9)
 
 
Unspecified(9)
 
 
 Related BioAssays
 Related BioAssays
AID: 393178
Data Source: ChEMBL (541207)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2014-08-23

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Heat shock 70 kDa protein 1A/1B; AltName: Full=Heat shock 70 kDa protein 1/2; Short=HSP70-1/HSP70-2; Short=HSP70.1/HSP70.2
Description ..   
Protein Family: Nucleotide-binding domain of HSPA1-A, -B, -L, HSPA-2, -6, -7, -8, and similar proteins
Comment ..   

Gene:HSPA1B     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum.

Abstract: Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC(50) values from 30 nM to 1.6 micrOM were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents.
(PMID: 19195901)
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
1Fold change activity commentFold change activity commentString
2Fold change standard flagFold change standard flagInteger
3Fold change qualifierFold change qualifierString
4Fold change published valueFold change published valueFloat
5Fold change standard valueFold change standard valueFloat

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