ArticleScientific reports2018
Identification and characterization of aspartyl-tRNA synthetase inhibitors against Mycobacterium tuberculosis by an integrated whole-cell target-based approach.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 25 citations in OpenAlex.
- Isoleucyl-tRNA synthetase depletion reveals vulnerabilities in Mycobacterium abscessus and Mycobacterium marinum.Communications biology · 2025Article
- Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aminoacyl tRNA Synthetases: Implications of Structural Biology in Drug Development against Trypanosomatid Parasites.ACS omega · 2023Review
- Sterically demanding macrocyclic Eu(iii) complexes for selective recognition of phosphate and real-time monitoring of enzymatically generated adenosine monophosphate.Chemical science · 2022Article
- Deep learning-driven prediction of drug mechanism of action from large-scale chemical-genetic interaction profiles.Journal of cheminformatics · 2022Article
- Failing upwards: Genetics-based strategies to improve antibiotic discovery and efficacy inFrontiers in cellular and infection microbiology · 2022Review
- An anti-tuberculosis compound screen using a zebrafish infection model identifies an aspartyl-tRNA synthetase inhibitor.Disease models & mechanisms · 2021Article
- Development of a novel secondary phenotypic screen to identify hits within the mycobacterial protein synthesis pipeline.FASEB bioAdvances · 2020Article
- Opportunities for OvercomingInternational journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis, the causative agent of tuberculosis, has surpassed HIV as the leading cause of death due to an infectious disease worldwide, being responsible for more than 1.5 million deaths in low-income countries. In response to a pandemic threat by drug resistant strains, the tuberculosis research community is searching for new chemical entities with novel mechanisms of action to avoid drug resistance and shorten treatment regimens using combinatorial chemotherapy. Herein, we have identified several novel chemical scaffolds, GSK97C (spiro-oxazolidin-2-one), GSK93A (2-amino-1,3-thiazole, GSK85A and GSK92A (enamides), which target M. tuberculosis aspartyl-tRNA synthetase (Mt-AspRS), an essential component of the protein synthesis machinery of tuberculosis, using a whole-cell target-based screening strategy against a genetically modified Mycobacterium bovis BCG strain. We also provide further evidence of protein inhibition and inhibitor profiling through a classical aminoacylation reaction and a tRNA-independent assay, respectively. Altogether, our results have identified a number of hit new molecules with novel mechanism of action for further development through medicinal chemistry as hits and leads.
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Registered trials
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