Thousands of chemical starting points for antimalarial lead identification
Francisco-Javier Gamo, Laura M Sanz, Jaume Vidal, Cristina de Cozar, Emilio Alvarez, Jose-Luis Lavandera, Dana E Vanderwall, Darren VS Green, Vinod Kumar, Samiul Hasan, James R Brown, Catherine E Peishoff, Lon R Cardon, Jose F Garcia-Bustos
NATURE | NATURE PUBLISHING GROUP | Published : 2010
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. Analy..View full abstract
We thank S. Peregrina and S. Prats for technical assistance, and D. Jimenez-Alfaro for supplying compounds pre-dispensed in microtitre plates. We thank P. Vallance and R. Keenan for organising support for this work, R. Macarron and J. Luengo for developing the IFI index and getting the chemistry data ready for publication, together with J. M. Fiandor, S. Chakravorty and members of GSK's Chemistry Council. J. Lewis, A. Clow, J. Overington and M. Davies were instrumental in the uploading and formatting of the data. We also thank N. Cammack, P. Sanseau and J. Burrows for critically commenting on the manuscript. The support and funding of Medicines for Malaria Venture is gratefully acknowledged.