Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: Identification of a New Chemical Class of Antimalarials, ACT-213615      
dateReleased:
07-19-2012
description:
The increasing spread of drug-resistant malaria strains underscores the need for new antimalarial agents with novel modes of action (MOAs). Here, we describe a compound representative of a new class of antimalarials. This molecule, ACT-213615, potently inhibits in vitro erythrocytic growth of all tested Plasmodium falciparum strains, irrespective of their drug resistance properties, with IC(50) values in the low single-digit nanomolar range. Like the clinically used artemisinins, the compound equally and very rapidly affects all three asexual erythrocytic parasite stages. In contrast, microarray studies suggest that the MOA of ACT-213615 is different from that of the artemisinins and other known antimalarials. ACT-213615 is orally bioavailable in mice, exhibits activity in the murine P. berghei model and efficacy comparable to that of the reference drug chloroquine in the recently established P. falciparum SCID mouse model.ACT-213615 represents a new class of potent antimalarials that merits further investigation for its clinical potential. Histone deacetylase (HDACs) inhibitors are being intensively pursued as potential new antimalarial drugs, and are also emerging as valuable tools for investigating transcriptional control in malaria parasites. In this study, the genome-wide transcriptional effects of three structurally related hydroxamate HDAC inhibitors were profiled in Plasmodium falciparum, the most lethal of the malaria parasite species that infects humans. Trophozoite-stage P. falciparum cells were treated with ACT-213615 for increasing amount of time at IC50 concentration and cells were harvested in parralled with DMSO treated controls for microarray-based transcriptional profiling.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-39485
refinement:
raw
alternateIdentifiers:
39485
keywords:
functional genomics
dateModified:
05-03-2014
availability:
available
types:
gene expression
name:
Plasmodium falciparum
ID:
A-GEOD-11248
name:
ZB/SBS-NTU Plasmodium falciparum 3D7 11.4K v1.1
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-39485/E-GEOD-39485.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-39485/E-GEOD-39485.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39485
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress