ArticleScience translational medicine2012
Structural basis for benzothiazinone-mediated killing of Mycobacterium tuberculosis.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 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
81 citing papers in PubMed, 216 citations in OpenAlex.
- Human prostaglandin reductases dearomatize and inactivate benzothiazinone antitubercular drugs.EMBO molecular medicine · 2026Article
- Mechanism of the M. tuberculosis DprE1-DprE2 epimerase complex and inhibition by anti-tubercular drugs.Nature chemical biology · 2026Article
- Covalent Inhibitors in Antimicrobial Drug Development-Beyond β-Lactams.Molecules (Basel, Switzerland) · 2026Review
- Covalent Inhibitors Targeting Mycobacterial Enzymes: Current Status, Challenges and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Thiadiazole-azetidinone sulfonamide hybrids with antimycobacterial activity supported by structure-based analysis.RSC advances · 2026Article
- Menaquinone depletion resensitises bedaquiline-resistant tuberculosis.bioRxiv : the preprint server for biology · 2026Article
- Exploring the Natural Products Atlas (NPAtlas) Database for Hunting Prospective Irreversible Covalent DprE1 Inhibitors With Antitubercular Activity: An IntegratedJournal of tropical medicine · 2026Article
- In-Silico Exploration of the StreptomeDB Database for Potential Irreversible DprE1 Inhibitors toward Antitubercular Treatment.ChemistryOpen · 2025Article
- TAK1 phosphorylation mediates macozinone (PBTZ169) induced innate immune activation against tuberculosis.mSphere · 2025Article
- Article
- Functions of nitroreductases in mycobacterial physiology and drug susceptibility.Journal of bacteriology · 2025Review
- The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis.Nature communications · 2025Article
- A Comparative Pharmacokinetics Study of Orally and Intranasally Administered 8-Nitro-1,3-benzothiazin-4-one (BTZ043) Amorphous Drug Nanoparticles.ACS pharmacology & translational science · 2024Article
- Novel Prodrug Strategies for the Treatment of Tuberculosis.Chemistry, an Asian journal · 2024Review
- Structure-based drug design and characterization of novel pyrazine hydrazinylidene derivatives with a benzenesulfonate scaffold as noncovalent inhibitors of DprE1 tor tuberculosis treatment.Molecular diversity · 2024Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Modulation of the Meisenheimer complex metabolism of nitro-benzothiazinones by targeted C-6 substitution.Communications chemistry · 2024Article
- Synthesis, Activity, Toxicity, and In Silico Studies of New AntimycobacterialPharmaceuticals (Basel, Switzerland) · 2024Article
- Development of New Drugs to Treat Tuberculosis Based on the Dinitrobenzamide Scaffold.Pharmaceuticals (Basel, Switzerland) · 2024Article
- A high-throughput target-based screening approach for the identification and assessment ofMicrobiology spectrum · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 4 countries.
Funding
Abstract
The benzothiazinone BTZ043 is a tuberculosis drug candidate with nanomolar whole-cell activity. BTZ043 targets the DprE1 catalytic component of the essential enzyme decaprenylphosphoryl-β-D-ribofuranose-2'-epimerase, thus blocking biosynthesis of arabinans, vital components of mycobacterial cell walls. Crystal structures of DprE1, in its native form and in a complex with BTZ043, reveal formation of a semimercaptal adduct between the drug and an active-site cysteine, as well as contacts to a neighboring catalytic lysine residue. Kinetic studies confirm that BTZ043 is a mechanism-based, covalent inhibitor. This explains the exquisite potency of BTZ043, which, when fluorescently labeled, localizes DprE1 at the poles of growing bacteria. Menaquinone can reoxidize the flavin adenine dinucleotide cofactor in DprE1 and may be the natural electron acceptor for this reaction in the mycobacterium. Our structural and kinetic analysis provides both insight into a critical epimerization reaction and a platform for structure-based design of improved inhibitors.
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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.