ArticleACS chemical biology2015
Mutations in the P-type cation-transporter ATPase 4, PfATP4, mediate resistance to both aminopyrazole and spiroindolone antimalarials.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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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
59 citing papers in PubMed, 99 citations in OpenAlex.
- Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated Plasmodium falciparum Malaria.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Review
- Mechanisms of PfDNMT2 inhibition and PfATP6-mediated resistance to the antimalarial candidate SC83288 in Plasmodium falciparum.Nature communications · 2026Article
- Endogenous structure of antimalarial target PfATP4 reveals an apicomplexan-specific P-type ATPase modulator.Nature communications · 2025Article
- Identification of α-Azacyclic Acetamide-Based Inhibitors ofACS infectious diseases · 2025Article
- PfATP2 is a flippase on the Plasmodium falciparum surface that is important for growth and influences parasite sensitivity to antiplasmodial compounds.PLoS pathogens · 2025Article
- Towards next-generation treatment options to combat Plasmodium falciparum malaria.Nature reviews. Microbiology · 2025Review
- Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4.ChemMedChem · 2024Article
- Systematic in vitro evolution inScience (New York, N.Y.) · 2024Article
- Chemoproteomics validates selective targeting ofeLife · 2024Article
- A pH Fingerprint Assay to Identify Inhibitors of Multiple Validated and Potential Antimalarial Drug Targets.ACS infectious diseases · 2024Article
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- Article
- Optimization of 2,3-Dihydroquinazolinone-3-carboxamides as Antimalarials Targeting PfATP4.Journal of medicinal chemistry · 2023Article
- Metabolic responses in blood-stage malaria parasites associated with increased and decreased sensitivity to PfATP4 inhibitors.Malaria journal · 2023Article
- Current and emerging target identification methods for novel antimalarials.International journal for parasitology. Drugs and drug resistance · 2022Review
- Uncovering the antimalarial potential of toad venoms through a bioassay-guided fractionation process.International journal for parasitology. Drugs and drug resistance · 2022Article
- Article
- A G358S mutation in the Plasmodium falciparum NaNature communications · 2022Article
- AssessmentAntimicrobial agents and chemotherapy · 2022Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Aminopyrazoles are a new class of antimalarial compounds identified in a cellular antiparasitic screen with potent activity against Plasmodium falciparum asexual and sexual stage parasites. To investigate their unknown mechanism of action and thus identify their target, we cultured parasites in the presence of a representative member of the aminopyrazole series, GNF-Pf4492, to select for resistance. Whole genome sequencing of three resistant lines showed that each had acquired independent mutations in a P-type cation-transporter ATPase, PfATP4 (PF3D7_1211900), a protein implicated as the novel Plasmodium spp. target of another, structurally unrelated, class of antimalarials called the spiroindolones and characterized as an important sodium transporter of the cell. Similarly to the spiroindolones, GNF-Pf4492 blocks parasite transmission to mosquitoes and disrupts intracellular sodium homeostasis. Our data demonstrate that PfATP4 plays a critical role in cellular processes, can be inhibited by two distinct antimalarial pharmacophores, and supports the recent observations that PfATP4 is a critical antimalarial target.
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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.