Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.
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Van Voorhis WC
Department of Medicine, Division of Allergy and Infectious Diseases, Center for Emerging and Reemerging Infectious Diseases (CERID), University of Washington, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA. Electronic address: wesley@uw.edu.
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Doggett JS
Portland VA Medical Center, Portland, OR 97239, USA.
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Parsons M
Department of Global Health, University of Washington, Seattle, WA 98195, USA; Center for Infectious Disease Research, Seattle, WA 98109, USA.
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Hulverson MA
Department of Medicine, Division of Allergy and Infectious Diseases, Center for Emerging and Reemerging Infectious Diseases (CERID), University of Washington, Seattle, WA 98109, USA.
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Choi R
Department of Medicine, Division of Allergy and Infectious Diseases, Center for Emerging and Reemerging Infectious Diseases (CERID), University of Washington, Seattle, WA 98109, USA.
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Arnold SLM
Department of Medicine, Division of Allergy and Infectious Diseases, Center for Emerging and Reemerging Infectious Diseases (CERID), University of Washington, Seattle, WA 98109, USA.
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Riggs MW
School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ 85721, USA.
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Hemphill A
Institute of Parasitology, Vetsuisse Faculty, University of Bern, Berne, Switzerland.
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Howe DK
Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
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Mealey RH
Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.
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Lau AOT
The National Institutes of Health, NIAID, DEA, 5601 Fishers Lane, Rockville, MD 20892, USA.
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Merritt EA
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
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Maly DJ
Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
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Fan E
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
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Ojo KK
Department of Medicine, Division of Allergy and Infectious Diseases, Center for Emerging and Reemerging Infectious Diseases (CERID), University of Washington, Seattle, WA 98109, USA. Electronic address: ojo67kk@u.washington.edu.
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Published in:
- Experimental parasitology. - 2017
English
Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium-dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this article, we review efficacy against the kinase target, parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped kinase inhibitors.
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Language
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Open access status
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green
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Identifiers
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Persistent URL
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https://folia.unifr.ch/global/documents/202018
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