ArticleNature communications2024
Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 14 citations in OpenAlex.
- Structure-Guided Optimization of Novel Inhibitors ofJournal of medicinal chemistry · 2026Article
- Potent reaction hijacking inhibitors ofbioRxiv : the preprint server for biology · 2026Article
- Identification of an Orally Efficacious Imidazo[4,5-Journal of medicinal chemistry · 2026Article
- Idler Compounds: A Simple Protocol for Openly Sharing Fridge Contents for Cross-Screening.Journal of medicinal chemistry · 2026Article
- tRNA Modification Landscapes in Streptococci: Shared Losses and Clade-Specific Adaptations.bioRxiv : the preprint server for biology · 2025Article
- Disruption of P. falciparum amino acid transporter elevates intracellular proline and induces resistance to Prolyl-tRNA synthetase inhibitors.Cell chemical biology · 2025Article
- Natural product-mediated reaction hijacking mechanism validates Plasmodium aspartyl-tRNA synthetase as an antimalarial drug target.PLoS pathogens · 2025Article
- Covalent inhibition ofiScience · 2025Article
- Towards next-generation treatment options to combat Plasmodium falciparum malaria.Nature reviews. Microbiology · 2025Review
- A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo.PLoS pathogens · 2024Article
Corrections and comments
- Update of
Authors and funding
44 authors at 18 institutions in 6 countries.
Funding
Abstract
Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.
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.