ArticleThe Journal of antibiotics2015
Discovery and characterization of a novel class of pyrazolopyrimidinedione tRNA synthesis inhibitors.
Article in The Journal of antibiotics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 18 citations in OpenAlex.
- Aminoisothiazolamides, a new class of potent inhibitors of lysyl-tRNA synthetase.Pest management science · 2025Article
- Overview on Strategies and Assays for Antibiotic Discovery.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Diversification of aminoacyl-tRNA synthetase activitiesFrontiers in physiology · 2022Review
- Lysyl-tRNA Synthetase fromSLAS discovery : advancing life sciences R & D · 2020Article
- Article
- Aminoacyl-tRNA Synthetases in the Bacterial World.EcoSal Plus · 2016Review
- Water Disinfection Byproducts Induce Antibiotic Resistance-Role of Environmental Pollutants in Resistance Phenomena.Environmental science & technology · 2016Article
- Are the physicochemical properties of antibacterial compounds really different from other drugs?Journal of cheminformatics · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A high-throughput phenotypic screen for novel antibacterial agents led to the discovery of a novel pyrazolopyrimidinedione, PPD-1, with preferential activity against methicillin-resistant Staphylococcus aureus (MRSA). Resistance mapping revealed the likely target of inhibition to be lysyl tRNA synthetase (LysRS). Preliminary structure-activity relationship (SAR) studies led to an analog, PPD-2, which gained Gram-negative antibacterial activity at the expense of MRSA activity and resistance to this compound mapped to prolyl tRNA synthetase (ProRS). These targets of inhibition were confirmed in vitro, with PPD-1 showing IC₅₀s of 21.7 and 35 μM in purified LysRS and ProRS enzyme assays, and PPD-2, 151 and 0.04 μM, respectively. The highly attractive chemical properties of these compounds combined with intriguing preliminary SAR suggest that further exploration of this compelling novel series is warranted.
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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.