ArticleProceedings of the National Academy of Sciences of the United States of America2014
(+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04709692 (An Open Label Phase 2a Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of), which is not on this map. Cited by 139 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
An Open Label Phase 2a Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of (+)-SJ000557733 (SJ733) With or Without Cobicistat in Adult Patients With Acute, Uncomplicated Malaria Over a 42 Day Period
Who cites it
139 citing papers in PubMed, 239 citations in OpenAlex.
- Combining SJ733, an oral ATP4 inhibitor of Plasmodium falciparum, with the pharmacokinetic enhancer cobicistat: An innovative approach in antimalarial drug development.EBioMedicine · 2022Trial
- 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
- A human microdose study of the antimalarial drug GSK3191607 in healthy volunteers.British journal of clinical pharmacology · 2018Trial
- Mechanistic perspectives on antimalarial agents: from FDA-approved drugs to next-generation candidates.RSC advances · 2026Review
- Potent acridone antimalarial against all three life stages of Plasmodium.Nature communications · 2026Article
- Natural triterpenic phenolic esters target PfA-M17 in Plasmodium falciparum.Malaria journal · 2026Article
- Impacts of Cipargamin on NaMembranes · 2025Article
- 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
- Structure-Activity Relationships of 3-Hydroxypropanamidines (HPAs) with Potent In Vivo Antimalarial Activity.Journal of medicinal chemistry · 2025Article
- Pathophysiological Associations and Measurement Techniques of Red Blood Cell Deformability.Biosensors · 2025Review
- An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs.Nature communications · 2025Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Optimization and Characterization of N-Acetamide Indoles as Antimalarials That Target PfATP4.Journal of medicinal chemistry · 2025Article
- Mutational analysis of an antimalarial drug target,Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TKK130 is a 3-Hydroxy-Propanamidine (HPA) with Potent AntimalarialJournal of medicinal chemistry · 2025Article
- Genome sequencing of Plasmodium malariae identifies continental segregation and mutations associated with reduced pyrimethamine susceptibility.Nature communications · 2024Article
- 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
79 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
50 authors at 12 institutions in 5 countries.
Funding
Abstract
Drug discovery for malaria has been transformed in the last 5 years by the discovery of many new lead compounds identified by phenotypic screening. The process of developing these compounds as drug leads and studying the cellular responses they induce is revealing new targets that regulate key processes in the Plasmodium parasites that cause malaria. We disclose herein that the clinical candidate (+)-SJ733 acts upon one of these targets, ATP4. ATP4 is thought to be a cation-transporting ATPase responsible for maintaining low intracellular Na(+) levels in the parasite. Treatment of parasitized erythrocytes with (+)-SJ733 in vitro caused a rapid perturbation of Na(+) homeostasis in the parasite. This perturbation was followed by profound physical changes in the infected cells, including increased membrane rigidity and externalization of phosphatidylserine, consistent with eryptosis (erythrocyte suicide) or senescence. These changes are proposed to underpin the rapid (+)-SJ733-induced clearance of parasites seen in vivo. Plasmodium falciparum ATPase 4 (pfatp4) mutations that confer resistance to (+)-SJ733 carry a high fitness cost. The speed with which (+)-SJ733 kills parasites and the high fitness cost associated with resistance-conferring mutations appear to slow and suppress the selection of highly drug-resistant mutants in vivo. Together, our data suggest that inhibitors of PfATP4 have highly attractive features for fast-acting antimalarials to be used in the global eradication campaign.
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What OpenQuestion holds
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.