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 review, we review efficacy against the kinase target, the parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped-kinase inhibitors.

Document Type

Article

Publication Date

9-2017

Notes/Citation Information

Published in Experimental Parasitology, v. 180, p. 71-83.

© 2017 Elsevier Inc. All rights reserved.

This manuscript version is made available under the CC‐BY‐NC‐ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.

The document available for download is the author's post-peer-review final draft of the article.

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.exppara.2017.01.001

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.

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