ArticleScience translational medicine2015
The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 108 citations in OpenAlex.
- Atomic-Level Structures Reveal How a Repurposed 3‑Aminopyrazine-2-carboxamide Scaffold InhibitsACS omega · 2026Article
- Febrifugine dihydrochloride restricts porcine epidemic diarrhea virus replication by modulating the IGF1R-driven PI3K/AKT-apoptosis axis.Journal of virology · 2026Article
- Gene Expression, Docking and Machine Learning in Malaria Drug Discovery: A Systematic Review.Biochemistry research international · 2026Review
- Disruption of P. falciparum amino acid transporter elevates intracellular proline and induces resistance to Prolyl-tRNA synthetase inhibitors.Cell chemical biology · 2025Article
- Halofuginone Disrupted Collagen Deposition via mTOR-eIF2α-ATF4 Axis to Enhance Chemosensitivity in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- tRNA regulation and amino acid usage bias reflect a coordinated metabolic adaptation iniScience · 2024Article
- ATP mimetics targeting prolyl-tRNA synthetases as a new avenue for antimalarial drug development.iScience · 2024Article
- Competitive Inhibition of Okanin againstInternational journal of molecular sciences · 2024Article
- The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.Cardiovascular diabetology · 2024Review
- Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A "One-Health" Concern.Life (Basel, Switzerland) · 2024Review
- Genetic crosses within and between species ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanism of Qingchang compound against coccidiosis based on network pharmacology-molecular docking.Frontiers in veterinary science · 2024Article
- Single-cell quantitative bioimaging ofmSphere · 2023Article
- Article
- Computational screening of FDA-approved drugs to identify potential TgDHFR, TgPRS, and TgCDPK1 proteins inhibitors against Toxoplasma gondii.Scientific reports · 2023Article
- Cytoplasmic isoleucyl tRNA synthetase as an attractive multistage antimalarial drug target.Science translational medicine · 2023Article
- Targeting prolyl-tRNA synthetase via a series of ATP-mimetics to accelerate drug discovery against toxoplasmosis.PLoS pathogens · 2023Article
- Transcriptome profile of halofuginone resistant and sensitive strains ofFrontiers in microbiology · 2023Article
- Promising antimalarial hits from phenotypic screens: a review of recently-described multi-stage actives and their modes of action.Frontiers in cellular and infection microbiology · 2023Review
- Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance.Nature communications · 2022Article
Corrections and comments
- Commented on by
Authors and funding
24 authors at 5 institutions in 1 country.
Funding
Abstract
The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for developing next-generation antimalarial drugs. Using an integrated chemogenomics approach that combined drug resistance selection, whole-genome sequencing, and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA (transfer RNA) synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivative halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the Plasmodium berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses and represents a promising lead for the development of dual-stage next-generation antimalarials.
Indexed as
Identifiers
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.