Journal article

Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.

  • 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.
  • Doggett JS Portland VA Medical Center, Portland, OR 97239, USA.
  • Parsons M Department of Global Health, University of Washington, Seattle, WA 98195, USA; Center for Infectious Disease Research, Seattle, WA 98109, USA.
  • 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.
  • 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.
  • 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.
  • Riggs MW School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ 85721, USA.
  • Hemphill A Institute of Parasitology, Vetsuisse Faculty, University of Bern, Berne, Switzerland.
  • Howe DK Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
  • Mealey RH Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7040, USA.
  • Lau AOT The National Institutes of Health, NIAID, DEA, 5601 Fishers Lane, Rockville, MD 20892, USA.
  • Merritt EA Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Maly DJ Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Fan E Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • 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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  • 2017-01-10
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.
Language
  • English
Open access status
green
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Persistent URL
https://folia.unifr.ch/global/documents/202018
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