Prioritization of Molecular Targets for Antimalarial Drug Discovery

Barbara Forte, Sabine Ottilie, Andrew Plater, Brice Campo, Koen J. Dechering, Francisco Javier Gamo, Daniel E. Goldberg, Eva S. Istvan, Marcus C. S. Lee, Amanda K. Lukens, Case W. McNamara, Jacquin Niles, John Okombo, Charisse Flerida A. Pasaje, Miles G. Siegel, Dyann F. Wirth, Susan Wyllie, David A. Fidock, Beatriz Baragaña (Lead / Corresponding author), Elizabeth A. Winzeler (Lead / Corresponding author)Ian H. Gilbert

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Abstract

There is a shift in antimalarial drug discovery from phenotypic screening toward target-based approaches, as more potential drug targets are being validated in Plasmodium species. Given the high attrition rate and high cost of drug discovery, it is important to select the targets most likely to deliver progressible drug candidates. In this paper, we describe the criteria that we consider important for selecting targets for antimalarial drug discovery. We describe the analysis of a number of drug targets in the Malaria Drug Accelerator (MalDA) pipeline, which has allowed us to prioritize targets that are ready to enter the drug discovery process. This selection process has also highlighted where additional data are required to inform target progression or deprioritization of other targets. Finally, we comment on how additional drug targets may be identified.

Original languageEnglish
Pages (from-to)2764-2776
Number of pages13
JournalACS Infectious Diseases
Volume7
Issue number10
Early online date15 Sep 2021
DOIs
Publication statusPublished - 8 Oct 2021

Keywords

  • malaria
  • Plasmodium
  • drug discovery
  • molecular targets

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