Thousands of chemical starting points for antimalarial lead identification View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-05

AUTHORS

Francisco-Javier Gamo, Laura M. Sanz, Jaume Vidal, Cristina de Cozar, Emilio Alvarez, Jose-Luis Lavandera, Dana E. Vanderwall, Darren V. S. Green, Vinod Kumar, Samiul Hasan, James R. Brown, Catherine E. Peishoff, Lon R. Cardon, Jose F. Garcia-Bustos

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. More... »

PAGES

305

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature09107

DOI

http://dx.doi.org/10.1038/nature09107

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009413566

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20485427


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