ArticleParasites & vectors2026
Nanoscaffold-based 3D human liver spheroids for predictive hepatotoxicity screening of antimalarial compounds from the global health priority box.
Article in Parasites & vectors, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDrug-induced liver injury (DILI) remains a significant barrier to the safe and efficient use of antimalarial medicines. Many promising compounds fail in late-stage development or post-marketing owing to unforeseen toxicity, particularly DILI. Incorporating a predictive hepatotoxicity assessment is therefore critical to reduce clinical risk and development costs. The Medicines for Malaria Venture (MMV) Global Health Priority Box (GHPB) provides a library of compounds with demonstrated or potential antimalarial activity, yet their hepatotoxicity risk remains poorly defined. Our early work developed and validated a nanoscaffold-based three-dimensional (3D) liver spheroid platform. Here, we apply this validated model for the first time to assess the hepatotoxicity of clinically used and candidate antimalarial GHPB compounds.
methodsOur validated nanoscaffold-based 3D liver spheroid platform was used to evaluate the hepatotoxicity of approved antimalarial drugs of known liver toxicity (quinine, primaquine, amodiaquine, sulfadoxine/pyrimethamine, and artemisinin) and six GHPB candidate compounds. Half maximal inhibitory concentration (IC
resultsOur nanoscaffold-based 3D liver spheroid platform accurately reproduced the known DILI rankings of the approved antimalarials, confirming its predictive validity. Using these referenced IC
conclusionsThis study demonstrates the translational application of a validated nanoscaffold-based 3D human liver spheroid model for antimalarial drug in vitro hepatotoxicity assessment. By establishing a reference framework from clinically approved antimalarials and applying it to candidate compounds from the MMV GHPB, our platform enabled early classification of hepatotoxicity risk using a human-relevant, non-animal method. The findings support the integration of advanced 3D in vitro systems into antimalarial drug discovery pipelines to improve safety prediction, reduce reliance on animal testing, and accelerate the development of safer, more effective antimalarial therapies.
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