Thousands of chemical starting points for antimalarial lead identification

Francisco-Javier Gamo, Laura M Sanz, Jaume Vidal, Cristina de Cozar, Emilio Alvarez-Ruiz, Jose L 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

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711 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)305 - 310
Number of pages6
JournalNature
Volume465
Issue number7296
DOIs
Publication statusPublished - 2010
Externally publishedYes

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