IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v465y2010i7296d10.1038_nature09107.html
   My bibliography  Save this article

Thousands of chemical starting points for antimalarial lead identification

Author

Listed:
  • Francisco-Javier Gamo

    (Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain)

  • Laura M. Sanz

    (Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain)

  • Jaume Vidal

    (Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain)

  • Cristina de Cozar

    (Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain)

  • Emilio Alvarez

    (Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain)

  • Jose-Luis Lavandera

    (Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain)

  • Dana E. Vanderwall

    (Computational and Structural Chemistry, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, North Carolina 27709-3398, USA)

  • Darren V. S. Green

    (Computational and Structural Chemistry, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Hertfordshire, Stevenage SG1 2NY, UK)

  • Vinod Kumar

    (Computational Biology, Quantitative Sciences, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA)

  • Samiul Hasan

    (Computational Biology, Quantitative Sciences, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA)

  • James R. Brown

    (Computational Biology, Quantitative Sciences, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA)

  • Catherine E. Peishoff

    (Computational and Structural Chemistry, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA)

  • Lon R. Cardon

    (Quantitative Sciences, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania 19406, USA)

  • Jose F. Garcia-Bustos

    (Tres Cantos Medicines Development Campus, GlaxoSmithKline, Severo Ochoa 2, 28760 Tres Cantos, Spain)

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 µM 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.

Suggested Citation

  • 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 &, 2010. "Thousands of chemical starting points for antimalarial lead identification," Nature, Nature, vol. 465(7296), pages 305-310, May.
    • Handle: RePEc:nat:nature:v:465:y:2010:i:7296:d:10.1038_nature09107
    DOI: 10.1038/nature09107
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature09107
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature09107?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Stanley C. Xie & Yinuo Wang & Craig J. Morton & Riley D. Metcalfe & Con Dogovski & Charisse Flerida A. Pasaje & Elyse Dunn & Madeline R. Luth & Krittikorn Kumpornsin & Eva S. Istvan & Joon Sung Park &, 2024. "Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Krittikorn Kümpornsin & Theerarat Kochakarn & Tomas Yeo & John Okombo & Madeline R. Luth & Johanna Hoshizaki & Mukul Rawat & Richard D. Pearson & Kyra A. Schindler & Sachel Mok & Heekuk Park & Anne-Ca, 2023. "Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Selina Bopp & Charisse Flerida A. Pasaje & Robert L. Summers & Pamela Magistrado-Coxen & Kyra A. Schindler & Victoriano Corpas-Lopez & Tomas Yeo & Sachel Mok & Sumanta Dey & Sebastian Smick & Armiyaw , 2023. "Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:465:y:2010:i:7296:d:10.1038_nature09107. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.