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- W2960320827 abstract "Abstract We developed a novel series of antimalarial compounds based on a 4-cyano-3-methylisoquinoline. Our lead compound MB14 achieved modest inhibition of the growth in vitro of the human malaria parasite, Plasmodium falciparum . To identify its biological target we selected for parasites resistant to MB14. Genome sequencing revealed that all resistant parasites bore a single point S374R mutation in the sodium (Na + ) efflux transporter PfATP4. There are many compounds known to inhibit PfATP4 and some are under preclinical development. MB14 was shown to inhibit Na + dependent ATPase activity in parasite membranes, consistent with the compound targeting PfATP4 directly. PfATP4 inhibitors cause swelling and lysis of infected erythrocytes, attributed to the accumulation of Na + inside the intracellular parasites and the resultant parasite swelling. We show here that inhibitor-induced lysis of infected erythrocytes is dependent upon the parasite protein RhopH2, a component of the new permeability pathways that are induced by the parasite in the erythrocyte membrane. These pathways mediate the influx of Na + into the infected erythrocyte and their suppression via RhopH2 knockdown limits the accumulation of Na + within the parasite hence protecting the infected erythrocyte from lysis. This study reveals a role for the parasite-induced new permeability pathways in the mechanism of action of PfATP4 inhibitors." @default.
- W2960320827 created "2019-07-23" @default.
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- W2960320827 date "2019-07-16" @default.
- W2960320827 modified "2023-10-15" @default.
- W2960320827 title "A 4-cyano-3-methylisoquinoline inhibitor of Plasmodium falciparum growth targets the sodium efflux pump PfATP4" @default.
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- W2960320827 cites W1972179890 @default.
- W2960320827 cites W1972736568 @default.
- W2960320827 cites W1978578424 @default.
- W2960320827 cites W1982332926 @default.
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- W2960320827 cites W2143048218 @default.
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- W2960320827 cites W2338020438 @default.
- W2960320827 cites W2528725597 @default.
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- W2960320827 doi "https://doi.org/10.1038/s41598-019-46500-5" @default.
- W2960320827 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6635429" @default.
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- W2960320827 hasPublicationYear "2019" @default.
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