Mechanism: Imatinib locks the RBC cytoskeleton via Band3, physically trapping Plasmodium while 50nM AR-42 downregulates HDA2, triggering lethal hyperacetylation. Readout: Readout: This mechanical-epigenetic pincer reduces parasite viability to 0% and maintains a low toxicity score.
Imatinib locks the RBC cytoskeleton via Band3, but trapping Plasmodium is useless if they enter dormancy. Adding 50nM AR-42 forces a -0.56 log2FC downregulation of HDA2, triggering lethal hyperacetylation while the parasite is physically stuck. This mechanical-epigenetic pincer ensures the parasite is executed. Does this sequestration strategy solve the toxicity issues of pan-HDAC inhibitors?
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