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The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Chemical genetics of Plasmodium falciparum

Open access
Guiguemde, W. Armand, Shelat, Anang A., Bouck, David, Duffy, Sandra, Crowther, Gregory J., Davis, Paul H., Smithson, David C., Connelly, Michele, Clark, Julie, Zhu, Fangyi, Jiménez-Díaz, María B., Martinez, María S., Wilson, Emily B., Tripathi, Abhai K., Gut, Jiri, Sharlow, Elizabeth R., Bathurst, Ian, Mazouni, Farah El, Fowble, Joseph W., Forquer, Isaac, McGinley, Paula L., Castro, Steve, Angulo-Barturen, Iñigo, Ferrer, Santiago, Rosenthal, Philip J., DeRisi, Joseph L., Sullivan, David J., Lazo, John S., Roos, David S., Riscoe, Michael K., Phillips, Margaret A., Rathod, Pradipsinh K., Van Voorhis, Wesley C., Avery, Vicky M., Guy, R. Kiplin·2010·Nature

Abstract

Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals. Here we disclose structures and biological activity of the entire library—many of which showed potent in vitro activity against drug-resistant P. falciparum strains—and detailed profiling of 172 representative candidates. A reverse chemical genetic study identified 19 new inhibitors of 4 validated drug targets and 15 novel binders among 61 malarial proteins. Phylochemogenetic profiling in several organisms revealed similarities between Toxoplasma gondii and mammalian cell lines and dissimilarities between P. falciparum and related protozoans. One exemplar compound displayed efficacy in a murine model. Our findings provide the scientific community with new starting points for malaria drug discovery.

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Metadata

Authors
Guiguemde, W. A., Shelat, A. A., Bouck, D., Duffy, S., Crowther, G. J., Davis, P. H., Smithson, D. C., Connelly, M., Clark, J., Zhu, F., Jiménez-Díaz, M. B., Martinez, M. S., Wilson, E. B., Tripathi, A. K., Gut, J., Sharlow, E. R., Bathurst, I., Mazouni, F. E., Fowble, J. W., Forquer, I., McGinley, P. L., Castro, S., Angulo-Barturen, I., Ferrer, S., Rosenthal, P. J., DeRisi, J. L., Sullivan, D. J., Lazo, J. S., Roos, D. S., Riscoe, M. K., Phillips, M. A., Rathod, P. K., Van Voorhis, W. C., Avery, V. M., & Guy, R. K.
Venue
Nature
Published
2010-05-20
Volume
465
Issue
7296
Pages
311-315
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1993795323
Cited by
566
References
2
FWCI
65.30
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Chemical genetics of Plasmodium falciparum. https://app.cochat.ai/papers/10.1038/nature09099
The paper
Guiguemde, W. A., Shelat, A. A., Bouck, D., Duffy, S., Crowther, G. J., Davis, P. H., Smithson, D. C., Connelly, M., Clark, J., Zhu, F., Jiménez-Díaz, M. B., Martinez, M. S., Wilson, E. B., Tripathi, A. K., Gut, J., Sharlow, E. R., Bathurst, I., Mazouni, F. E., Fowble, J. W., . . . Guy, R. K. (2010). Chemical genetics of Plasmodium falciparum. Nature. https://doi.org/10.1038/nature09099

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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