A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria

Author:

Phillips Margaret A.1,Lotharius Julie2,Marsh Kennan3,White John4,Dayan Anthony2,White Karen L.5,Njoroge Jacqueline W.1,El Mazouni Farah1,Lao Yanbin3,Kokkonda Sreekanth4,Tomchick Diana R.6,Deng Xiaoyi1,Laird Trevor2,Bhatia Sangeeta N.7,March Sandra7,Ng Caroline L.8,Fidock David A.89,Wittlin Sergio1011,Lafuente-Monasterio Maria12,Benito Francisco Javier Gamo12,Alonso Laura Maria Sanz12,Martinez Maria Santos12,Jimenez-Diaz Maria Belen12,Bazaga Santiago Ferrer12,Angulo-Barturen Iñigo12,Haselden John N.12,Louttit James13,Cui Yi13,Sridhar Arun13,Zeeman Anna-Marie14,Kocken Clemens14,Sauerwein Robert15,Dechering Koen15,Avery Vicky M.16,Duffy Sandra16,Delves Michael17,Sinden Robert17,Ruecker Andrea17,Wickham Kristina S.18,Rochford Rosemary18,Gahagen Janet19,Iyer Lalitha19,Riccio Ed19,Mirsalis Jon19,Bathhurst Ian2,Rueckle Thomas2,Ding Xavier2,Campo Brice2,Leroy Didier2,Rogers M. John20,Rathod Pradipsinh K.4,Burrows Jeremy N.2,Charman Susan A.5

Affiliation:

1. Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Boulevard, Dallas, TX 75390–9041, USA.

2. Medicines for Malaria Venture, 1215 Geneva, Switzerland.

3. Abbvie, 1 North Waukegan Road, North Chicago, IL 60064–6104, USA.

4. Departments of Chemistry and Global Health, University of Washington, Seattle, WA 98195, USA.

5. Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

6. Department of Biophysics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390–9041, USA.

7. Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

8. Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.

9. Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.

10. Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.

11. University of Basel, 4003 Basel, Switzerland.

12. GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.

13. GSK, Park Road, Ware, Hertfordshire SG12 0DP, UK.

14. Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, Netherlands.

15. TropIQ Health Sciences, 6525 GA Nijmegen, Netherlands.

16. Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.

17. Imperial College of Science Technology and Medicine, London SW7 2AY, UK.

18. State University of New York Upstate Medical University, Syracuse, NY 13210, USA.

19. SRI International, Menlo Park, CA 94025, USA.

20. National Institutes for Allergy and Infectious Diseases, 6610 Rockledge Drive, Bethesda, MD 20892, USA.

Abstract

The antimalarial drug DSM265 displays activity against blood and liver stages of Plasmodium falciparum and has a long predicted half-life in humans.

Funder

U.S. NIH

Welch Foundation

Wellcome Trust

Medicines for Malaria Venture (MMV)

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Reference66 articles.

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