ArticleNature communications2016
Identification of KasA as the cellular target of an anti-tubercular scaffold.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 96 citations in OpenAlex.
- Free energy perturbation and machine learning-assisted identification of novel molecules for the Mycobacterium tuberculosis KasA protein: a fragment-based drug design approach.Molecular diversity · 2026Article
- Contribution of Proteins to Membrane and Cell Wall Structures in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Recent Characterization of Key Proteins to Combat Tuberculosis.Advances in experimental medicine and biology · 2026Review
- Structural isomerisation affects the antitubercular activity of adamantyl-isoxyl adducts.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Targeting Mycolic Acid Biosynthesis with Cyclic Sulfamates: A New Strategy againstACS infectious diseases · 2025Article
- Integration of multi-modal measurements identifies critical mechanisms of tuberculosis drug action.Cell systems · 2025Article
- The KasA inhibitor JSF-3285 improves the sterilizing activity of bedaquiline-pretomanid-containing regimens in a mouse model of tuberculosis.Antimicrobial agents and chemotherapy · 2025Article
- Azetidines Kill Multidrug-ResistantJournal of medicinal chemistry · 2024Article
- Discovery of novel reversible inhibitor of DprE1 based on benzomorpholine for the treatment of tuberculosis.Microbiology spectrum · 2023Article
- Review
- Target Identification in Anti-Tuberculosis Drug Discovery.International journal of molecular sciences · 2023Review
- Emerging Extracellular Molecular Targets for Innovative Pharmacological Approaches to Resistant Mtb Infection.Biomolecules · 2023Review
- A Review of Fatty Acid Biosynthesis Enzyme Inhibitors as Promising Antimicrobial Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Review
- 1,3-Diarylpyrazolyl-acylsulfonamides Target HadAB/BC Complex inACS infectious diseases · 2022Article
- The Role of Phosphorylation and Acylation in the Regulation of Drug Resistance inBiomedicines · 2022Review
- Fragment-Based Drug Discovery against Mycobacteria: The Success and Challenges.International journal of molecular sciences · 2022Review
- The emerging role of mass spectrometry-based proteomics in drug discovery.Nature reviews. Drug discovery · 2022Review
- Hit Compounds and Associated Targets in IntracellularMolecules (Basel, Switzerland) · 2022Article
- CRISPRi chemical genetics and comparative genomics identify genes mediating drug potency in Mycobacterium tuberculosis.Nature microbiology · 2022Article
- Integrated genomics and chemical biology herald an era of sophisticated antibacterial discovery, from defining essential genes to target elucidation.Cell chemical biology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 5 institutions in 5 countries.
Funding
Abstract
Phenotypic screens for bactericidal compounds are starting to yield promising hits against tuberculosis. In this regard, whole-genome sequencing of spontaneous resistant mutants generated against an indazole sulfonamide (GSK3011724A) identifies several specific single-nucleotide polymorphisms in the essential Mycobacterium tuberculosis β-ketoacyl synthase (kas) A gene. Here, this genomic-based target assignment is confirmed by biochemical assays, chemical proteomics and structural resolution of a KasA-GSK3011724A complex by X-ray crystallography. Finally, M. tuberculosis GSK3011724A-resistant mutants increase the in vitro minimum inhibitory concentration and the in vivo 99% effective dose in mice, establishing in vitro and in vivo target engagement. Surprisingly, the lack of target engagement of the related β-ketoacyl synthases (FabH and KasB) suggests a different mode of inhibition when compared with other Kas inhibitors of fatty acid biosynthesis in bacteria. These results clearly identify KasA as the biological target of GSK3011724A and validate this enzyme for further drug discovery efforts against tuberculosis.
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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.