Extended-spectrum antiprotozoal bumped kinase inhibitors: A review

Wesley C. Van Voorhis, J. Stone Doggett, Marilyn Parsons, Matthew A. Hulverson, Ryan Choi, Samuel L.M. Arnold, Michael W. Riggs, Andrew Hemphill, Daniel K. Howe, Robert H. Mealey, Audrey O.T. Lau, Ethan A. Merritt, Dustin J. Maly, Erkang Fan, Kayode K. Ojo

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)71-83
Number of pages13
JournalExperimental Parasitology
Volume180
DOIs
StatePublished - Sep 2017

Keywords

  • Bumped kinase inhibitors
  • Calcium-dependent protein kinase
  • Gatekeeper residue

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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    Van Voorhis, W. C., Doggett, J. S., Parsons, M., Hulverson, M. A., Choi, R., Arnold, S. L. M., Riggs, M. W., Hemphill, A., Howe, D. K., Mealey, R. H., Lau, A. O. T., Merritt, E. A., Maly, D. J., Fan, E., & Ojo, K. K. (2017). Extended-spectrum antiprotozoal bumped kinase inhibitors: A review. Experimental Parasitology, 180, 71-83. https://doi.org/10.1016/j.exppara.2017.01.001