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- W3174475674 abstract "During malaria infections, there is a significant increase in the pentose phosphate pathway activity of Plasmodium falciparum (1). In addition, its key enzyme, glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase (PfGluPho), shows structural differences to the human enzyme, thus making PfGluPho an ideal target for antimalarial drug design (2). Recent cloning and overexpression (2) of recombinant PfGluPho allowed investigations in a high throughput format. We were able to develop a high-throughput screening assay to identify inhibitors for PfGluPho. Three small molecule compound libraries were screened, namely LOPAC™ (Sigma-Aldrich, 1,280 compounds), Spectrum™ (Microsource discovery system, ~2,000 compounds), and DIVERSet™ (ChemBridge, ~50,000 compounds), which resulted in ~900 compounds that inhibited PfGluPho activity for at least 50%. Selected compounds were subjected to follow-up studies, including IC50 determination and mechanistic characterization. The availability of recombinant PfGluPho, its major differences to human G6PD, and the identified inhibitors facilitate further studies on PfGluPho as excellent drug target candidates for the search of new antimalarial drugs. Supported by NIH 1R21AI082434-01" @default.
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- W3174475674 date "2012-04-01" @default.
- W3174475674 modified "2023-09-27" @default.
- W3174475674 title "High‐throughput screening for Plasmodium falciparum glucose‐6‐phosphate dehydrogenase‐6‐phosphogluconolactonase inhibitors" @default.
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- W3174475674 doi "https://doi.org/10.1096/fasebj.26.1_supplement.964.2" @default.
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