2. Academic Validation
  3. A novel protein kinase is essential in bloodstream Trypanosoma brucei

A novel protein kinase is essential in bloodstream Trypanosoma brucei

  • Int J Parasitol. 2016 Jul;46(8):479-83. doi: 10.1016/j.ijpara.2016.03.001.
Bryan C Jensen 1,  Nick Booster 1,  Rama Subba Rao Vidadala 2,  Dustin J Maly 3,  Marilyn Parsons 4
Affiliations

Affiliations

  • 1 Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, 307 Westlake Ave. N., Seattle, WA 98109, USA.
  • 2 Dept. of Chemistry, University of Washington, Seattle, WA 98195, USA.
  • 3 Dept. of Chemistry, University of Washington, Seattle, WA 98195, USA; Dept. of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • 4 Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, 307 Westlake Ave. N., Seattle, WA 98109, USA; Dept. of Global Health, University of Washington, Seattle, WA 98195, USA. Electronic address: [email protected].
PMID: 27018127 DOI: 10.1016/j.ijpara.2016.03.001
Abstract

Human African trypanosomiasis a fatal disease for which no vaccines exist and treatment regimens are difficult. Here, we evaluate a Trypanosoma brucei protein kinase, AEK1, as a potential drug target. Conditional knockouts confirmed AEK1 essentiality in bloodstream forms. For chemical validation, we overcame the lack of AEK1 inhibitors by creating parasites expressing a single, functional analog-sensitive AEK1 allele. Analog treatment of mice infected with this strain delayed parasitemia and death, with one-third of Animals showing no parasitemia. These studies validate AEK1 as a drug target and highlight the need for further understanding of its function.

Keywords

AGC kinase; Analog-sensitive; Drug target; In vivo; Protein kinase; Trypanosome.

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    Product Name
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  • HY-13942
    99.28%, Src Inhibitor
    Src