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

doi:10.1016/j.exppara.2017.01.001

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

Veterinary Science

Research output: Contribution to journal › Article › peer-review

41 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 language	English
Pages (from-to)	71-83
Number of pages	13
Journal	Experimental Parasitology
Volume	180
DOIs	https://doi.org/10.1016/j.exppara.2017.01.001
State	Published - Sep 2017

Bibliographical note

Funding Information:
This work was supported by the US National Institutes of Health (NICHHD R01HD080670 & NIAID R01AI111341, R01AI089441) and the USDA (2014-06183). This work was also supported by Swiss National Science Foundation (grant No. 310030_165782) and in part by Career Development Award # BX002440 to J. Stone Doggett from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development.

Publisher Copyright:
© 2017 Elsevier Inc.

Keywords

Bumped kinase inhibitors
Calcium-dependent protein kinase
Gatekeeper residue

ASJC Scopus subject areas

Parasitology
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.exppara.2017.01.001

Cite this

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

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AU - Choi, Ryan

AU - Arnold, Samuel L.M.

AU - Riggs, Michael W.

AU - Hemphill, Andrew

AU - Howe, Daniel K.

AU - Mealey, Robert H.

AU - Lau, Audrey O.T.

AU - Merritt, Ethan A.

AU - Maly, Dustin J.

AU - Fan, Erkang

AU - Ojo, Kayode K.

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Extended-spectrum antiprotozoal bumped kinase inhibitors: A review

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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