Spiroindolones, a Potent Compound Class for the Treatment of Malaria

  • Matthias Rottmann
    Swiss Tropical and Public Health Institute, Parasite Chemotherapy, CH-4002 Basel, Switzerland.
  • Case McNamara
    Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
  • Bryan K. S. Yeung
    Novartis Institute for Tropical Diseases, 138670 Singapore.
  • Marcus C. S. Lee
    Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
  • Bin Zou
    Novartis Institute for Tropical Diseases, 138670 Singapore.
  • Bruce Russell
    Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648, Singapore.
  • Patrick Seitz
    Swiss Tropical and Public Health Institute, Parasite Chemotherapy, CH-4002 Basel, Switzerland.
  • David M. Plouffe
    Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
  • Neekesh V. Dharia
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Jocelyn Tan
    Novartis Institute for Tropical Diseases, 138670 Singapore.
  • Steven B. Cohen
    Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
  • Kathryn R. Spencer
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gonzalo E. González-Páez
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Suresh B. Lakshminarayana
    Novartis Institute for Tropical Diseases, 138670 Singapore.
  • Anne Goh
    Novartis Institute for Tropical Diseases, 138670 Singapore.
  • Rossarin Suwanarusk
    Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648, Singapore.
  • Timothy Jegla
    Department of Biology and Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
  • Esther K. Schmitt
    Natural Products Unit, Novartis Pharma AG, CH-4002 Basel, Switzerland.
  • Hans-Peter Beck
    Swiss Tropical and Public Health Institute, Parasite Chemotherapy, CH-4002 Basel, Switzerland.
  • Reto Brun
    Swiss Tropical and Public Health Institute, Parasite Chemotherapy, CH-4002 Basel, Switzerland.
  • Francois Nosten
    Shoklo Malaria Research Unit, Mae Sot, Tak 63110, Thailand.
  • Laurent Renia
    Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648, Singapore.
  • Veronique Dartois
    Novartis Institute for Tropical Diseases, 138670 Singapore.
  • Thomas H. Keller
    Novartis Institute for Tropical Diseases, 138670 Singapore.
  • David A. Fidock
    Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
  • Elizabeth A. Winzeler
    Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
  • Thierry T. Diagana
    Novartis Institute for Tropical Diseases, 138670 Singapore.

書誌事項

公開日
2010-09-03
DOI
  • 10.1126/science.1193225
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:title>Antimalarial Drug Candidate</jats:title> <jats:p> Spiroindolones were discovered as promising antimalarial drug candidates through a high-throughput screening approach that should be applicable to a range of neglected infectious diseases. <jats:bold> Rottmann <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1175" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1193225">1175</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5996" page="1153" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1194923">Wells</jats:related-article> </jats:bold> ) present the preclinical profile for an optimized spiroindolone drug candidate, NITD609. They obtained evidence for a decrease in drug sensitivity in strains of the malaria parasite <jats:italic>Plasmodium falciparum</jats:italic> bearing amino acid mutations in the P-type ATPase, indicating possible mechanisms of action and/or resistance. </jats:p>

収録刊行物

  • Science

    Science 329 (5996), 1175-1180, 2010-09-03

    American Association for the Advancement of Science (AAAS)

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