ArticleNature chemical biology2013
Antituberculosis thiophenes define a requirement for Pks13 in mycolic acid biosynthesis.
Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 159 citations in OpenAlex.
- Large-Scale Chemical-Genetic Interaction Profiling Identifies a Small-Molecule Inhibitor ofACS infectious diseases · 2026Article
- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- Exquisite specificity of Pks13 defines the essentiality of trehalose in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Biosynthetic Pathway of Mycolic Acids: Dual-Function Targets for Tuberculosis Therapeutics and Green Steroid Drugs Biomanufacturing.Pharmaceutics · 2025Review
- Divergent transcriptional regulation of redox-homeostasis and permeability modulate rifampicin tolerance and sensitivity in Mycobacterium tuberculosis.Nature communications · 2025Article
- Article
- Synthesis and evaluation of Trehalose-Pks13 inhibitor conjugates targeting mycobacteria.Carbohydrate research · 2025Article
- Genetic and Cheminformatic Characterization ofACS infectious diseases · 2025Article
- Identification of a Series Containing a Pentafluorophenyl Moiety That Targets Pks13 to Inhibit Growth ofACS infectious diseases · 2025Article
- Structure-based Virtual Screening and Hit Identification of Novel designed Quinazolin-4(3H)-one Derivatives as Antitubercular Agent against TargetsCurrent drug discovery technologies · 2025Article
- Cryo-electron microscopy structure of the di-domain core ofMicrobiology (Reading, England) · 2024Article
- Inhibitors of the Thioesterase Activity ofACS infectious diseases · 2024Article
- Unlocking Opportunities forACS infectious diseases · 2024Review
- Polyketide Synthase 13 (Pks13) Inhibition: A Potential Target for New Class of Anti-tubercular Agents.Current topics in medicinal chemistry · 2024Review
- Repurposing an Antioxidant to KillBiomolecules · 2023Article
- Identification and Optimization of Novel Inhibitors of the Polyketide Synthase 13 Thioesterase Domain with Antitubercular Activity.Journal of medicinal chemistry · 2023Article
- Article
- Structural basis for the development of potential inhibitors targeting FadD23 from Mycobacterium tuberculosis.Acta crystallographica. Section F, Structural biology communications · 2023Article
- Therapeutic potential of coumestan Pks13 inhibitors for tuberculosis.Antimicrobial agents and chemotherapy · 2023Article
- An integrated computational approach towards novel drugs discovery against polyketide synthase 13 thioesterase domain of Mycobacterium tuberculosis.Scientific reports · 2023Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
We report a new class of thiophene (TP) compounds that kill Mycobacterium tuberculosis by the previously uncharacterized mechanism of Pks13 inhibition. An F79S mutation near the catalytic Ser55 site in Pks13 conferred TP resistance in M. tuberculosis. Overexpression of wild-type Pks13 resulted in TP resistance, and overexpression of the Pks13(F79S) mutant conferred high resistance. In vitro, TP inhibited fatty acyl-AMP loading onto Pks13. TP inhibited mycolic acid biosynthesis in wild-type M. tuberculosis, but it did so to a much lesser extent in TP-resistant M. tuberculosis. TP treatment was bactericidal and equivalent to treatment with the first-line drug isoniazid, but it was less likely to permit emergent resistance. Combined isoniazid and TP treatment resulted in sterilizing activity. Computational docking identified a possible TP-binding groove within the Pks13 acyl carrier protein domain. This study confirms that M. tuberculosis Pks13 is required for mycolic acid biosynthesis, validates it as a druggable target and demonstrates the therapeutic potential of simultaneously inhibiting multiple targets in the same biosynthetic pathway.
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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.