Thousands of chemical starting points for antimalarial lead identification
Top Cited Papers
- 1 May 2010
- journal article
- research article
- Published by Springer Nature in Nature
- Vol. 465 (7296) , 305-310
- https://doi.org/10.1038/nature09107
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 mu M 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.Keywords
This publication has 34 references indexed in Scilit:
- Drugging the Plasmodium kinome: the benefits of academia–industry synergyTrends in Pharmacological Sciences, 2008
- In vitro evaluations of antimalarial drugs and their relevance to clinical outcomesInternational Journal for Parasitology, 2008
- The effects of anti-bacterials on the malaria parasite Plasmodium falciparumMolecular and Biochemical Parasitology, 2007
- High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screeningArchives of Toxicology, 2006
- Components of Successful Lead GenerationCurrent Topics in Medicinal Chemistry, 2005
- A genomic perspective of protein kinases in Plasmodium falciparumProteins-Structure Function and Bioinformatics, 2004
- Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryoteBMC Genomics, 2004
- The Protein Kinase Complement of the Human GenomeScience, 2002
- Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparumNature, 2000
- A Plastid of Probable Green Algal Origin in Apicomplexan ParasitesScience, 1997