Plasmodial Kinase Inhibitors: License to Cure?

Journal of Medicinal Chemistry
Diego González CabreraKelly Chibale

Abstract

Advances in the genetics, function, and stage-specificity of Plasmodium kinases has driven robust efforts to identify targets for the design of antimalarial therapies. Reverse genomics following phenotypic screening against Plasmodia or related parasites has uncovered vulnerable kinase targets including PI4K, PKG, and GSK-3, an approach bolstered by access to human disease-directed kinase libraries. Alternatively, screening compound libraries against Plasmodium kinases has successfully led to inhibitors with antiplasmodial activity. As with other therapeutic areas, optimizing compound ADMET and PK properties in parallel with target inhibitory potency and whole cell activity becomes paramount toward advancing compounds as clinical candidates. These and other considerations will be discussed in the context of progress achieved toward deriving important, novel mode-of-action kinase-inhibiting antimalarial medicines.

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Citations

Feb 13, 2019·FEMS Microbiology Reviews·Amy L BurnsDanny W Wilson
Apr 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana Carolina C de SousaTimothy J Egan
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Methods Mentioned

BETA
X-ray
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pulldown
ubiquitination
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Mega7

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