ArticleAntimicrobial agents and chemotherapy2016
Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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
69 citing papers in PubMed, 118 citations in OpenAlex.
- A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial.Nature medicine · 2024Trial
- First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment.Antimicrobial agents and chemotherapy · 2019Trial
- The ZN domain acts as a dynamic switch coordinating multiple-step aminoacylation in bacterial leucyl-tRNA synthetase.Nucleic acids research · 2026Article
- Euglena gracilis as a high-throughput screening platform for antibacterial activity, cytotoxicity and membrane permeability in a one-step and cost-effective assay.The Journal of antibiotics · 2026Article
- Metalloids: Semi as Metals yet Full of Antimicrobial Potential.ChemMedChem · 2026Review
- Integrative computational approaches, molecular docking, and dynamic simulations reveal the antimycobacterial activity of fisetin as a potential inhibitor of Mycobacterium tuberculosis.Journal of computer-aided molecular design · 2026Article
- Combined Oral Contraceptive Drug-Drug Interaction Study With Ganfeborole, a New Anti-Tuberculosis Agent.Journal of clinical pharmacology · 2026Article
- Emerging therapeutic drug targets in amino acid and protein biosynthesis pathways against ESKAPE and non-ESKAPE pathogens: a comprehensive review.Archives of microbiology · 2026Review
- Selectivity of the Time-DependentACS chemical biology · 2025Article
- Recent Advancements in the Diversification and Applications of Boron-Containing Compounds in Medicinal Chemistry.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Total Synthesis of Kavaratamides A-C and Unnatural Analogs.ACS omega · 2025Article
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
- Article
- An open-access dashboard to interrogate the genetic diversity of Mycobacterium tuberculosis clinical isolates.Scientific reports · 2024Article
- Efficacy of epetraborole againstAntimicrobial agents and chemotherapy · 2024Article
- Targeting a microbiotaScience advances · 2024Article
- Insights into the Effects of Ligand Binding on Leucyl-tRNA Synthetase Inhibitors for Tuberculosis: In Silico Analysis and Isothermal Titration Calorimetry Validation.Biomolecules · 2024Article
- Exploiting thiol-functionalized benzosiloxaboroles for achieving diverse substitution patterns - synthesis, characterization and biological evaluation of promising antibacterial agents.RSC medicinal chemistry · 2024Article
- Identification and optimization of pyridine carboxamide-based scaffold as a drug lead forAntimicrobial agents and chemotherapy · 2024Article
- Laboratory Evolution of Antimicrobial Resistance in Bacteria to Develop Rational Treatment Strategies.Antibiotics (Basel, Switzerland) · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
37 authors at 7 institutions in 3 countries.
Funding
Abstract
The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of Mycobacterium tuberculosis highlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminoglycosides are a key component of therapy for multidrug-resistant TB, the oxazolidinone linezolid is the only orally available protein synthesis inhibitor that is effective against TB. Here, we show that small-molecule inhibitors of aminoacyl-tRNA synthetases (AARSs), which are known to be excellent antibacterial protein synthesis targets, are orally bioavailable and effective against M. tuberculosis in TB mouse infection models. We applied the oxaborole tRNA-trapping (OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), to M. tuberculosis LeuRS. X-ray crystallography was used to guide the design of LeuRS inhibitors that have good biochemical potency and excellent whole-cell activity against M. tuberculosis Importantly, their good oral bioavailability translates into in vivo efficacy in both the acute and chronic mouse models of TB with potency comparable to that of the frontline drug isoniazid.
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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.