Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.

Van Voorhis, Wesley C; Doggett, J Stone; Parsons, Marilyn; Hulverson, Matthew A; Choi, Ryan; Arnold, Samuel; Riggs, Michael W; Hemphill, Andrew; Howe, Daniel K; Mealey, Robert H; Lau, Audrey O T; Merritt, Ethan A; Maly, Dustin J; Fan, Erkang; Ojo, Kayode K (2017). Extended-spectrum antiprotozoal bumped kinase inhibitors: A review. Experimental parasitology, 180, pp. 71-83. Elsevier 10.1016/j.exppara.2017.01.001

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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.

Item Type:

Journal Article (Review Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology

ISSN:

0014-4894

Publisher:

Elsevier

Language:

English

Submitter:

Andrew Hemphill

Date Deposited:

28 Jul 2017 11:14

Last Modified:

16 Aug 2018 15:46

Publisher DOI:

10.1016/j.exppara.2017.01.001

PubMed ID:

28065755

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.96641

URI:

https://boris.unibe.ch/id/eprint/96641

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