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Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.

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.

SUBMITTER: Van Voorhis WC

PROVIDER: S-EPMC5498274 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Extended-spectrum antiprotozoal bumped kinase inhibitors: A review.

Van Voorhis Wesley C WC Doggett J Stone JS Parsons Marilyn M Hulverson Matthew A MA Choi Ryan R Arnold Samuel L M SLM Riggs Michael W MW Hemphill Andrew A Howe Daniel K DK Mealey Robert H RH Lau Audrey O T AOT Merritt Ethan A EA Maly Dustin J DJ Fan Erkang E Ojo Kayode K KK

Experimental parasitology 20170105

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 ar ...[more]

PMID: 28065755

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