ArticleNature communications2020
Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study.Journal of clinical pharmacology · 2025Trial
- The long and winding road: On the endoplasmic reticulum of Plasmodium and implications for pathogenesis.PLoS pathogens · 2026Review
- Plasmodium falciparum HSP90 inhibitors show divergent resistance despite a shared ATP-binding site.Cell reports · 2026Article
- Single-cell analysis ofbioRxiv : the preprint server for biology · 2026Article
- Article
- Shared Binding Site but Divergent Resistance Profiles Uncover Novel Resistance Mechanisms inbioRxiv : the preprint server for biology · 2025Article
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- Plasmodiumfalciparum protein kinase 6 and hemozoin formation are inhibited by a type II human kinase inhibitor exhibiting antimalarial activity.Cell chemical biology · 2025Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Innovations in Antimalarial Drug Discovery: New Targets and Leads.Current drug targets · 2025Review
- Uncovering the Mechanism of Action of Antiprotozoal Agents: A Survey on Photoaffinity Labeling Strategy.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Eliminating malaria transmission requires targeting immature and mature gametocytes through lipoidal uptake of antimalarials.Nature communications · 2024Article
- In vitro evaluation of ganaplacide/lumefantrine combination against Plasmodium falciparum in a context of artemisinin resistance.The Journal of antimicrobial chemotherapy · 2024Article
- An endoplasmic reticulum localized acetyl-CoA transporter is required for efficient fatty acid synthesis inOpen biology · 2024Article
- Plasmodium SEY1 is a novel druggable target that contributes to imidazolopiperazine mechanism of action.Research square · 2024Article
- Article
- Comparative chemical genomics inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Single-cell quantitative bioimaging ofmSphere · 2023Article
- Article
- Human nuclear hormone receptor activity contributes to malaria parasite liver stage development.Cell chemical biology · 2023Article
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 4 countries.
Funding
Abstract
A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.