ArticlePloS one2011
Plasmodium falciparum parasites are killed by a transition state analogue of purine nucleoside phosphorylase in a primate animal model.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 69 citations in OpenAlex.
- TargetingFrontiers in microbiology · 2026Review
- The human malaria-Antimicrobial agents and chemotherapy · 2024Review
- Identification and structural validation of purine nucleoside phosphorylase from Plasmodium falciparum as a target of MMV000848.The Journal of biological chemistry · 2024Article
- Phosphate Binding in PNP Alters Transition-State Analogue Affinity and Subunit Cooperativity.Biochemistry · 2023Article
- Xanthine oxidase levels and immune dysregulation are independently associated with anemia in Plasmodium falciparum malaria.Scientific reports · 2023Article
- Inhibition and Mechanism ofACS chemical biology · 2022Article
- Computer-Aided Drug Design (CADD) to De-Orphanize Marine Molecules: Finding Potential Therapeutic Agents for Neurodegenerative and Cardiovascular Diseases.Marine drugs · 2022Article
- An Uninvited Seat at the Dinner Table: How Apicomplexan Parasites Scavenge Nutrients from the Host.Microorganisms · 2021Review
- Novel Purine Chemotypes with Activity againstPharmaceuticals (Basel, Switzerland) · 2021Article
- Antiviral and Antimicrobial Nucleoside Derivatives: Structural Features and Mechanisms of Action.Molecular biology · 2021Article
- Impact of Field Isolate Identified Nonsynonymous Single Nucleotide Polymorphisms onACS infectious diseases · 2020Article
- Nucleoside Hydrolase NH 36: A Vital Enzyme for theFrontiers in immunology · 2019Review
- Enzymatic Transition States and Drug Design.Chemical reviews · 2018Review
- Genetic resistance to purine nucleoside phosphorylase inhibition inProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Immucillins in Infectious Diseases.ACS infectious diseases · 2018Review
- Intracellular rebinding of transition-state analogues provides extendedThe Journal of biological chemistry · 2017Article
- Identification of a novel putative inhibitor of the Plasmodium falciparum purine nucleoside phosphorylase: exploring the purine salvage pathway to design new antimalarial drugs.Molecular diversity · 2017Article
- Alternatives to currently used antimalarial drugs: in search of a magic bullet.Infectious diseases of poverty · 2016Review
- Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum.Acta crystallographica. Section F, Structural biology communications · 2016Article
- Substrate and Inhibitor Specificity of the Plasmodium berghei Equilibrative Nucleoside Transporter Type 1.Molecular pharmacology · 2016Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Plasmodium falciparum causes most of the one million annual deaths from malaria. Drug resistance is widespread and novel agents against new targets are needed to support combination-therapy approaches promoted by the World Health Organization. Plasmodium species are purine auxotrophs. Blocking purine nucleoside phosphorylase (PNP) kills cultured parasites by purine starvation. DADMe-Immucillin-G (BCX4945) is a transition state analogue of human and Plasmodium PNPs, binding with picomolar affinity. Here, we test BCX4945 in Aotus primates, an animal model for Plasmodium falciparum infections. Oral administration of BCX4945 for seven days results in parasite clearance and recrudescence in otherwise lethal infections of P. falciparum in Aotus monkeys. The molecular action of BCX4945 is demonstrated in crystal structures of human and P. falciparum PNPs. Metabolite analysis demonstrates that PNP blockade inhibits purine salvage and polyamine synthesis in the parasites. The efficacy, oral availability, chemical stability, unique mechanism of action and low toxicity of BCX4945 demonstrate potential for combination therapies with this novel antimalarial agent.
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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.