ArticleEMBO molecular medicine2014
Towards a new combination therapy for tuberculosis with next generation benzothiazinones.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
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Who cites it
148 citing papers in PubMed, 380 citations in OpenAlex.
- Human prostaglandin reductases dearomatize and inactivate benzothiazinone antitubercular drugs.EMBO molecular medicine · 2026Article
- Discovery of potent DprE1-targeted antitubercular agents: synthesis and evaluation of PBTZ169/TBA7371-based derivatives.Molecular diversity · 2026Article
- Mechanism of the M. tuberculosis DprE1-DprE2 epimerase complex and inhibition by anti-tubercular drugs.Nature chemical biology · 2026Article
- Oral milk exosome-PLGA nanoparticles enhance anti-tuberculosis efficacy of PBTZ169 and bedaquiline.iScience · 2026Article
- Covalent Inhibitors Targeting Mycobacterial Enzymes: Current Status, Challenges and Future Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pardon the interruption: how Und-P sequestration has reshaped our understanding of the bacterial cell envelope.Journal of bacteriology · 2026Review
- Design, synthesis and antitubercular evaluation of novel 5,6-diphenyl-1,2,4-triazine-piperazine derivatives targeting mycobacterial dihydrofolate reductase.ADMET & DMPK · 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
- Scaffold Hopping in Tuberculosis Drug Discovery: Principles, Applications, and Case Studies.Journal of medicinal chemistry · 2025Review
- Pyrazolopyridine pyrimidone hybrids as potential DprE1 inhibitors, design, synthesis and biological evaluation as antitubercular agents.Scientific reports · 2025Article
- Translational Modeling of BTZ-043 to Predict Phase 2A Efficacy and Evaluate Drug-Drug Interactions With Bedaquiline, Pretomanid, and Linezolid in Murine Models.The Journal of infectious diseases · 2025Article
- Review
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
- Functions of nitroreductases in mycobacterial physiology and drug susceptibility.Journal of bacteriology · 2025Review
- Real-time evaluation of macozinone activity againstAntimicrobial agents and chemotherapy · 2025Article
- Contribution of telacebec to novel drug regimens in a murine tuberculosis model.Antimicrobial agents and chemotherapy · 2025Article
- The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis.Nature communications · 2025Article
- Activity of combinations of bactericidal and bacteriostatic compounds inFrontiers in microbiology · 2025Review
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The benzothiazinone lead compound, BTZ043, kills Mycobacterium tuberculosis by inhibiting the essential flavo-enzyme DprE1, decaprenylphosphoryl-beta-D-ribose 2-epimerase. Here, we synthesized a new series of piperazine-containing benzothiazinones (PBTZ) and show that, like BTZ043, the preclinical candidate PBTZ169 binds covalently to DprE1. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Compared to BTZ043, PBTZ169 has improved potency, safety and efficacy in zebrafish and mouse models of tuberculosis (TB). When combined with other TB drugs, PBTZ169 showed additive activity against M. tuberculosis in vitro except with bedaquiline (BDQ) where synergy was observed. A new regimen comprising PBTZ169, BDQ and pyrazinamide was found to be more efficacious than the standard three drug treatment in a murine model of chronic disease. PBTZ169 is thus an attractive drug candidate to treat TB in humans.
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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.