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Research ArticleMalaria
A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria
- Margaret A. Phillips1,*,
- Julie Lotharius2,
- Kennan Marsh3,
- John White4,
- Anthony Dayan2,
- Karen L. White5,
- Jacqueline W. Njoroge1,
- Farah El Mazouni1,
- Yanbin Lao3,
- Sreekanth Kokkonda4,
- Diana R. Tomchick6,
- Xiaoyi Deng1,
- Trevor Laird2,
- Sangeeta N. Bhatia7,
- Sandra March7,
- Caroline L. Ng8,
- David A. Fidock8,9,
- Sergio Wittlin10,11,
- Maria Lafuente-Monasterio12,
- Francisco Javier Gamo Benito12,
- Laura Maria Sanz Alonso12,
- Maria Santos Martinez12,
- Maria Belen Jimenez-Diaz12,
- Santiago Ferrer Bazaga12,
- Iñigo Angulo-Barturen12,
- John N. Haselden12,
- James Louttit13,
- Yi Cui13,
- Arun Sridhar13,
- Anna-Marie Zeeman14,
- Clemens Kocken14,
- Robert Sauerwein15,
- Koen Dechering15,
- Vicky M. Avery16,
- Sandra Duffy16,
- Michael Delves17,
- Robert Sinden17,
- Andrea Ruecker17,
- Kristina S. Wickham18,
- Rosemary Rochford18,
- Janet Gahagen19,
- Lalitha Iyer19,
- Ed Riccio19,
- Jon Mirsalis19,
- Ian Bathhurst2,
- Thomas Rueckle2,
- Xavier Ding2,
- Brice Campo2,
- Didier Leroy2,
- M. John Rogers20,
- Pradipsinh K. Rathod4,
- Jeremy N. Burrows2 and
- Susan A. Charman5,*
- 1Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Boulevard, Dallas, TX 75390–9041, USA.
- 2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
- 3Abbvie, 1 North Waukegan Road, North Chicago, IL 60064–6104, USA.
- 4Departments of Chemistry and Global Health, University of Washington, Seattle, WA 98195, USA.
- 5Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
- 6Department of Biophysics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390–9041, USA.
- 7Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
- 8Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
- 9Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
- 10Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.
- 11University of Basel, 4003 Basel, Switzerland.
- 12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
- 13GSK, Park Road, Ware, Hertfordshire SG12 0DP, UK.
- 14Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, Netherlands.
- 15TropIQ Health Sciences, 6525 GA Nijmegen, Netherlands.
- 16Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
- 17Imperial College of Science Technology and Medicine, London SW7 2AY, UK.
- 18State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
- 19SRI International, Menlo Park, CA 94025, USA.
- 20National Institutes for Allergy and Infectious Diseases, 6610 Rockledge Drive, Bethesda, MD 20892, USA.
- ↵*Corresponding author. E-mail: margaret.phillips{at}utsouthwestern.edu (M.A.P.); susan.charman{at}monash.edu (S.A.C.)
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Science Translational Medicine 15 Jul 2015:
Vol. 7, Issue 296, pp. 296ra111
DOI: 10.1126/scitranslmed.aaa6645
Vol. 7, Issue 296, pp. 296ra111
DOI: 10.1126/scitranslmed.aaa6645
Margaret A. Phillips
1Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Boulevard, Dallas, TX 75390–9041, USA.
Julie Lotharius
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
Kennan Marsh
3Abbvie, 1 North Waukegan Road, North Chicago, IL 60064–6104, USA.
John White
4Departments of Chemistry and Global Health, University of Washington, Seattle, WA 98195, USA.
Anthony Dayan
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
Karen L. White
5Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Jacqueline W. Njoroge
1Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Boulevard, Dallas, TX 75390–9041, USA.
Farah El Mazouni
1Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Boulevard, Dallas, TX 75390–9041, USA.
Yanbin Lao
3Abbvie, 1 North Waukegan Road, North Chicago, IL 60064–6104, USA.
Sreekanth Kokkonda
4Departments of Chemistry and Global Health, University of Washington, Seattle, WA 98195, USA.
Diana R. Tomchick
6Department of Biophysics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390–9041, USA.
Xiaoyi Deng
1Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Boulevard, Dallas, TX 75390–9041, USA.
Trevor Laird
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
Sangeeta N. Bhatia
7Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sandra March
7Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Caroline L. Ng
8Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
David A. Fidock
8Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
9Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
Sergio Wittlin
10Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.
11University of Basel, 4003 Basel, Switzerland.
Maria Lafuente-Monasterio
12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
Francisco Javier Gamo Benito
12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
Laura Maria Sanz Alonso
12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
Maria Santos Martinez
12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
Maria Belen Jimenez-Diaz
12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
Santiago Ferrer Bazaga
12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
Iñigo Angulo-Barturen
12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
John N. Haselden
12GlaxoSmithKline (GSK), Tres Cantos Medicines Development Campus, Severo Ochoa, Madrid 28760, Spain.
James Louttit
13GSK, Park Road, Ware, Hertfordshire SG12 0DP, UK.
Yi Cui
13GSK, Park Road, Ware, Hertfordshire SG12 0DP, UK.
Arun Sridhar
13GSK, Park Road, Ware, Hertfordshire SG12 0DP, UK.
Anna-Marie Zeeman
14Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, Netherlands.
Clemens Kocken
14Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, Netherlands.
Robert Sauerwein
15TropIQ Health Sciences, 6525 GA Nijmegen, Netherlands.
Koen Dechering
15TropIQ Health Sciences, 6525 GA Nijmegen, Netherlands.
Vicky M. Avery
16Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
Sandra Duffy
16Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia.
Michael Delves
17Imperial College of Science Technology and Medicine, London SW7 2AY, UK.
Robert Sinden
17Imperial College of Science Technology and Medicine, London SW7 2AY, UK.
Andrea Ruecker
17Imperial College of Science Technology and Medicine, London SW7 2AY, UK.
Kristina S. Wickham
18State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Rosemary Rochford
18State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Janet Gahagen
19SRI International, Menlo Park, CA 94025, USA.
Lalitha Iyer
19SRI International, Menlo Park, CA 94025, USA.
Ed Riccio
19SRI International, Menlo Park, CA 94025, USA.
Jon Mirsalis
19SRI International, Menlo Park, CA 94025, USA.
Ian Bathhurst
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
Thomas Rueckle
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
Xavier Ding
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
Brice Campo
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
Didier Leroy
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
M. John Rogers
20National Institutes for Allergy and Infectious Diseases, 6610 Rockledge Drive, Bethesda, MD 20892, USA.
Pradipsinh K. Rathod
4Departments of Chemistry and Global Health, University of Washington, Seattle, WA 98195, USA.
Jeremy N. Burrows
2Medicines for Malaria Venture, 1215 Geneva, Switzerland.
Susan A. Charman
5Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
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