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Thousands of chemical starting points for antimalarial lead identification.
- Source :
-
Nature [Nature] 2010 May 20; Vol. 465 (7296), pp. 305-10. - Publication Year :
- 2010
-
Abstract
- Malaria is a devastating infection caused by protozoa of the genus Plasmodium. Drug resistance is widespread, no new chemical class of antimalarials has been introduced into clinical practice since 1996 and there is a recent rise of parasite strains with reduced sensitivity to the newest drugs. We screened nearly 2 million compounds in GlaxoSmithKline's chemical library for inhibitors of P. falciparum, of which 13,533 were confirmed to inhibit parasite growth by at least 80% at 2 microM concentration. More than 8,000 also showed potent activity against the multidrug resistant strain Dd2. Most (82%) compounds originate from internal company projects and are new to the malaria community. Analyses using historic assay data suggest several novel mechanisms of antimalarial action, such as inhibition of protein kinases and host-pathogen interaction related targets. Chemical structures and associated data are hereby made public to encourage additional drug lead identification efforts and further research into this disease.
- Subjects :
- Animals
Antimalarials chemistry
Antimalarials toxicity
Cell Line, Tumor
Drug Resistance, Multiple drug effects
Humans
Malaria, Falciparum parasitology
Models, Biological
Phylogeny
Plasmodium falciparum enzymology
Plasmodium falciparum genetics
Plasmodium falciparum growth & development
Small Molecule Libraries chemistry
Small Molecule Libraries toxicity
Antimalarials analysis
Antimalarials pharmacology
Drug Discovery
Malaria, Falciparum drug therapy
Plasmodium falciparum drug effects
Small Molecule Libraries analysis
Small Molecule Libraries pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 465
- Issue :
- 7296
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 20485427
- Full Text :
- https://doi.org/10.1038/nature09107