ArticleAntimicrobial agents and chemotherapy2015
A novel inhibitor of gyrase B is a potent drug candidate for treatment of tuberculosis and nontuberculosis mycobacterial infections.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 81 citations in OpenAlex.
- Randomized study of the efficacy, safety, and pharmacokinetics of SPR720 for the treatment of Mycobacterium avium complex pulmonary disease.Scientific reports · 2026Trial
- Discovery of Putative GyrB Inhibitors againstCurrent medicinal chemistry · 2026Article
- Current Advances in Developing New Antimicrobial Agents Against Non-TuberculousAntibiotics (Basel, Switzerland) · 2025Review
- Review
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
- Microbial-based natural products as potential inhibitors targeting DNA gyrase B ofFrontiers in chemistry · 2025Article
- Revealing the Interaction Mechanism betweenInternational journal of molecular sciences · 2024Article
- Tackling Nontuberculous Mycobacteria by Repurposable Drugs and Potential Leads from Natural Products.Current topics in medicinal chemistry · 2024Review
- Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection.Acta pharmaceutica Sinica. B · 2023Article
- TargetingRSC medicinal chemistry · 2023Review
- Antibiotics in the clinical pipeline as of December 2022.The Journal of antibiotics · 2023Review
- Novel Synergies and Isolate Specificities in the Drug Interaction Landscape of Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2023Article
- Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets.International journal of molecular sciences · 2023Review
- Developments in Non-Intercalating Bacterial Topoisomerase Inhibitors: Allosteric and ATPase Inhibitors of DNA Gyrase and Topoisomerase IV.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Activity of Tricyclic Pyrrolopyrimidine Gyrase B Inhibitor against Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2022Article
- Spiropyrimidinetrione DNA Gyrase Inhibitors with Potent and Selective Antituberculosis Activity.Journal of medicinal chemistry · 2022Article
- Potential therapeutic targets fromRSC medicinal chemistry · 2022Review
- Nontuberculous Mycobacterial Resistance to Antibiotics and Disinfectants: Challenges Still Ahead.BioMed research international · 2022Review
- "Upcycling" known molecules and targets for drug-resistant TB.Frontiers in cellular and infection microbiology · 2022Article
- Anti-Mycobacterial Drug Resistance in Japan: How to Approach This Problem?Antibiotics (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New drugs to treat drug-resistant tuberculosis are urgently needed. Extensively drug-resistant and probably the totally drug-resistant tuberculosis strains are resistant to fluoroquinolones like moxifloxacin, which target gyrase A, and most people infected with these strains die within a year. In this study, we found that a novel aminobenzimidazole, VXc-486, which targets gyrase B, potently inhibits multiple drug-sensitive isolates and drug-resistant isolates of Mycobacterium tuberculosis in vitro (MICs of 0.03 to 0.30 μg/ml and 0.08 to 5.48 μg/ml, respectively) and reduces mycobacterial burdens in lungs of infected mice in vivo. VXc-486 is active against drug-resistant isolates, has bactericidal activity, and kills intracellular and dormant M. tuberculosis bacteria in a low-oxygen environment. Furthermore, we found that VXc-486 inhibits the growth of multiple strains of Mycobacterium abscessus, Mycobacterium avium complex, and Mycobacterium kansasii (MICs of 0.1 to 2.0 μg/ml), as well as that of several strains of Nocardia spp. (MICs of 0.1 to 1.0 μg/ml). We made a direct comparison of the parent compound VXc-486 and a phosphate prodrug of VXc-486 and showed that the prodrug of VXc-486 had more potent killing of M. tuberculosis than did VXc-486 in vivo. In combination with other antimycobacterial drugs, the prodrug of VXc-486 sterilized M. tuberculosis infection when combined with rifapentine-pyrazinamide and bedaquiline-pyrazinamide in a relapse infection study in mice. Furthermore, the prodrug of VXc-486 appeared to perform at least as well as the gyrase A inhibitor moxifloxacin. These findings warrant further development of the prodrug of VXc-486 for the treatment of tuberculosis and nontuberculosis mycobacterial infections.
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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.