Collateral hypersensitivity between ZY19489 and piperaquine neutralizes PfCRT-mediated drug efflux and Plasmodium falciparum resistance.

doi:10.1038/s41467-026-70914-1

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Article

Collateral hypersensitivity between ZY19489 and piperaquine neutralizes PfCRT-mediated drug efflux and Plasmodium falciparum resistance.

Nature communications - 1 Apr 2026

Okombo John, Ndiaye Tolla, Qahash Tarrick, Moura Igor M R, Gil-Iturbe Eva, Hagenah Laura M, Bridgford Jessica L, Bonatto Vinicius, Ward Kurt E, Yeo Tomas, Narwal Sunil K, Orta Lily V, Anderson Isla, Dhingra Satish K, Pasaje Charisse Flerida A, Park Heekuk, Kim Jonathan, Guido Rafael V C, Jiménez-Diaz Maria Belén, Angulo-Barturen Iñigo, Niles Jacquin C, Mancia Filippo, Uhlemann Anne-Catrin, Mok Sachel, Quick Matthias, Winzeler Elizabeth A, Leroy Didier, Llinás Manuel, Thathy Vandana, Fidock David A

Abstract excerpt

New antimalarial drugs are needed to combat the current emergence and spread of Plasmodium falciparum parasite resistance to artemisinin-based combination therapies. Here, we characterize ZY19489, a triaminopyrimidine presently in a Phase Ib clinical trial. Asexual blood-stage parasites pressured with ZY19489 acquire low-grade resistance, mediated by a novel mutation in the P. falciparum chloroquine resistance...

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Identifiers

PMID: 41922323
DOI: 10.1038/s41467-026-70914-1
PMCID: PMC13280021

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