ArticleNature2015
A novel multiple-stage antimalarial agent that inhibits protein synthesis.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 249 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
249citing papers in PubMed, 1 pooled it
48.6field-weighted citation impact, top 1% of its field
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
249 citing papers in PubMed, 1 synthesis or guideline pooled it, 454 citations in OpenAlex.
- Reproducibility of malaria sporozoite challenge model in humans for evaluating efficacy of vaccines and drugs: a systematic review.BMC infectious diseases · 2021Pooled it
- Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study.The Lancet. Infectious diseases · 2021Trial
- Development of Semisynthetic Blasticidin S Analogs with Potent and Fast-Killing Antimalarial Activity.ACS infectious diseases · 2026Article
- Identification and Evaluation of Dibasic Piperidines as Cell Wall Inhibitors againstACS infectious diseases · 2026Article
- Potent reaction hijacking inhibitors ofbioRxiv : the preprint server for biology · 2026Article
- Global-scale population genetic analysis of Plasmodium falciparum identifies region-specific patterns of malaria parasite adaptation.Nature communications · 2026Article
- Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development.Parasites & vectors · 2026Review
- Mechanistic perspectives on antimalarial agents: from FDA-approved drugs to next-generation candidates.RSC advances · 2026Review
- Antimalarial cabamiquine inhibits blood-stage of different field isolates of Plasmodium species.BMC infectious diseases · 2026Article
- Collateral hypersensitivity between ZY19489 and piperaquine neutralizes PfCRT-mediated drug efflux and Plasmodium falciparum resistance.Nature communications · 2026Article
- Identification and Evaluation of dibasic piperidines as novel cell wall inhibitors againstbioRxiv : the preprint server for biology · 2026Article
- Phenotypic profiling of Pathogen Box compounds MMV667494 and MMV028694 in bloodstream-formExperimental biology and medicine (Maywood, N.J.) · 2026Article
- Article
- A Novel Antimalarial Agent that Inhibits Protein Synthesis in Plasmodium falciparum.Angewandte Chemie (International ed. in English) · 2025Article
- Article
- Integrated structural biology of the native malarial translation machinery and its inhibition by an antimalarial drug.Nature structural & molecular biology · 2025Article
- Computationally guided optimization of the antimalarial activity and physicochemical properties of 2,4-diaminopyrimidines.RSC medicinal chemistry · 2025Article
- MappingbioRxiv : the preprint server for biology · 2025Article
- Structure-Activity Relationships of 3-Hydroxypropanamidines (HPAs) with Potent In Vivo Antimalarial Activity.Journal of medicinal chemistry · 2025Article
- Application of new approach methodologies for nonclinical safety assessment of drug candidates.Nature reviews. Drug discovery · 2025Review
189 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
65 authors at 15 institutions in 7 countries.
Beatriz BaragañaDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Irene HallyburtonDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Marcus C S LeeDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Neil R NorcrossDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Raffaella GrimaldiDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Thomas D OttoMalaria Programme, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
William R ProtoMalaria Programme, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
Andrew M BlagboroughDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
Stephan MeisterUniversity of California, San Diego, School of Medicine, 9500 Gilman Drive 0760, La Jolla, California 92093, USA.
Grennady WirjanataGlobal Health and Tropical Medicine Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, Darwin, Northern Territory 0811, Australia.
Andrea RueckerDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
Leanna M UptonDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
Tara S AbrahamDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Mariana J AlmeidaDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Anupam PradhanDepartment of Global Health, College of Public Health University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, Florida 33612, USA.
Achim PorzelleDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Torsten Luksch
María Santos MartínezGlaxoSmithKline, Tres Cantos Medicines Development Campus-Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Torsten Luksch
Judith M BolscherTropIQ Health Sciences, Geert Grooteplein 28, Huispost 268, 6525 GA Nijmegen, The Netherlands.
Andrew WoodlandDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Suzanne NorvalDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Fabio ZuccottoDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
John ThomasDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Frederick SimeonsDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Laste StojanovskiDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Maria Osuna-CabelloDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Paddy M BrockDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
Tom S ChurcherDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
Katarzyna A SalaDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
Sara E ZakutanskyDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
María Belén Jiménez-DíazGlaxoSmithKline, Tres Cantos Medicines Development Campus-Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Laura Maria SanzGlaxoSmithKline, Tres Cantos Medicines Development Campus-Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Jennifer RileyDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Rajshekhar BasakDepartment of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Michael CampbellCentre for Drug Candidate Optimisation, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Vicky M AveryEskitis Institute, Brisbane Innovation Park, Nathan Campus, Griffith University, Queensland 4111, Australia.
Robert W SauerweinTropIQ Health Sciences, Geert Grooteplein 28, Huispost 268, 6525 GA Nijmegen, The Netherlands.
Koen J DecheringTropIQ Health Sciences, Geert Grooteplein 28, Huispost 268, 6525 GA Nijmegen, The Netherlands.
Rintis NoviyantiMalaria Pathogenesis Laboratory, Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, 10430 Jakarta, Indonesia.
Brice CampoMedicines for Malaria Venture, PO Box 1826, 20 route de Pre-Bois, 1215 Geneva 15, Switzerland.
Julie A FrearsonDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Iñigo Angulo-BarturenGlaxoSmithKline, Tres Cantos Medicines Development Campus-Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Santiago Ferrer-BazagaGlaxoSmithKline, Tres Cantos Medicines Development Campus-Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Francisco Javier GamoGlaxoSmithKline, Tres Cantos Medicines Development Campus-Diseases of the Developing World, Severo Ochoa 2, Tres Cantos 28760, Madrid, Spain.
Paul G WyattDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Didier LeroyMedicines for Malaria Venture, PO Box 1826, 20 route de Pre-Bois, 1215 Geneva 15, Switzerland.
Peter SieglMedicines for Malaria Venture, PO Box 1826, 20 route de Pre-Bois, 1215 Geneva 15, Switzerland.
Michael J DelvesDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
Dennis E KyleDepartment of Global Health, College of Public Health University of South Florida, 3720 Spectrum Boulevard, Suite 304, Tampa, Florida 33612, USA.
Sergio WittlinSwiss Tropical and Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland.
Jutta MarfurtGlobal Health and Tropical Medicine Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, Darwin, Northern Territory 0811, Australia.
Ric N Price1] Global Health and Tropical Medicine Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, Casuarina, Darwin, Northern Territory 0811, Australia [2] Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LJ, UK.
Robert E SindenDepartment of Life Sciences, Imperial College, London SW7 2AZ, UK.
Elizabeth A WinzelerUniversity of California, San Diego, School of Medicine, 9500 Gilman Drive 0760, La Jolla, California 92093, USA.
Susan A CharmanCentre for Drug Candidate Optimisation, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
Lidiya BebrevskaMedicines for Malaria Venture, PO Box 1826, 20 route de Pre-Bois, 1215 Geneva 15, Switzerland.
David W GrayDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Simon CampbellMedicines for Malaria Venture, PO Box 1826, 20 route de Pre-Bois, 1215 Geneva 15, Switzerland.
Alan H FairlambDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Paul A WillisMedicines for Malaria Venture, PO Box 1826, 20 route de Pre-Bois, 1215 Geneva 15, Switzerland.
Julian C RaynerMalaria Programme, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
David A Fidock1] Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA [2] Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Kevin D ReadDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Ian H GilbertDrug Discovery Unit, Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
University of Dundee · GBImperial College London · GBGlaxoSmithKline (Spain) · ESMedicines for Malaria Venture · CHColumbia University · USTropIQ Health Sciences · NLWellcome Sanger Institute · GBMenzies School of Health Research · AUMonash University · AUUniversity of California, San Diego · USUniversity of South Florida · USCharles Darwin University · AUEijkman Institute for Molecular Biology · IDGriffith University · AUSwiss Tropical and Public Health Institute · CH
Funding
Discovery of chemically validated malaria liver stage targetsR01AI090141 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WINZELER, ELIZABETH A · 2011 to 2019
$3.4MDefining the targets of broad intervention antimalarial agentsR01AI103058 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WINZELER, ELIZABETH A · 2013 to 2016
$2.6MMedical Research Council MR/K010174/1NIAID NIH HHS R01 AI090141NIAID NIH HHS R01 AI103058Wellcome Trust 079838Wellcome Trust 091625Wellcome Trust 098051Wellcome Trust 100476
Abstract
There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.
Indexed as
AnimalsAntimalarialsDrug DiscoveryFemaleGene Expression RegulationLife Cycle StagesLiverMalariaMaleModels, MolecularPeptide Elongation Factor 2PlasmodiumPlasmodium bergheiPlasmodium falciparumPlasmodium vivaxProtein BiosynthesisAntimalarialsDDD107498Peptide Elongation Factor 2Quinolines
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.