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The antimalarial ef...
The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957
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- Miguel-Blanco, Celia (författare)
- Global Health, GlaxoSmithKline, Tres Cantos, Madrid, Spain
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- Murithi, James M. (författare)
- Department of Microbiology and Immunology, Columbia University Irving Medical Center, NY, New York, United States
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- Benavente, Ernest Diez (författare)
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
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- Angrisano, Fiona (författare)
- Division of Microbiology and Parasitology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, United Kingdom
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- Sala, Katarzyna A. (författare)
- Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom
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- van Schalkwyk, Donelly A. (författare)
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
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- Vanaerschot, Manu (författare)
- Department of Microbiology and Immunology, Columbia University Irving Medical Center, NY, New York, United States
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- Schwach, Frank (författare)
- Parasites and Microbes Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
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- Fuchter, Matthew J. (författare)
- Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, White City Campus, Wood Lane, London, United Kingdom
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- Billker, Oliver (författare)
- Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Parasites and Microbes Programme, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
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- Sutherland, Colin J. (författare)
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
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- Campino, Susana G. (författare)
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
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- Clark, Taane G. (författare)
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
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- Blagborough, Andrew M. (författare)
- Division of Microbiology and Parasitology, Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, United Kingdom; Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom
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- Fidock, David A. (författare)
- Department of Microbiology and Immunology, Columbia University Irving Medical Center, NY, New York, United States; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, NY, New York, United States
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- Herreros, Esperanza (författare)
- Global Health, GlaxoSmithKline, Tres Cantos, Madrid, Spain; Medicines for Malaria Venture, 20 Route de Pré-Bois, Geneva 15, Switzerland
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- Gamo, Francisco Javier (författare)
- Global Health, GlaxoSmithKline, Tres Cantos, Madrid, Spain
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- Baum, Jake (författare)
- Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom
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- Delves, Michael J. (författare)
- Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
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(creator_code:org_t)
- 2021-01-21
- 2021
- Engelska.
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957—a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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Miguel-Blanco, C ...
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Murithi, James M ...
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Benavente, Ernes ...
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Angrisano, Fiona
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Sala, Katarzyna ...
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van Schalkwyk, D ...
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visa fler...
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Vanaerschot, Man ...
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Schwach, Frank
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Fuchter, Matthew ...
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Billker, Oliver
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Sutherland, Coli ...
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Campino, Susana ...
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Clark, Taane G.
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Blagborough, And ...
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Fidock, David A.
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Herreros, Espera ...
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Gamo, Francisco ...
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Baum, Jake
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Delves, Michael ...
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