Advancements in Tuberculosis and Mycobacterial Infections Treatment: The Role of Gyrase B Inhibitor VXc-486

3 June 2024
The development of new treatments for drug-resistant tuberculosis (TB) is critical due to the rising prevalence of strains that are resistant to fluoroquinolones, such as moxifloxacin. VXc-486, a newly discovered aminobenzimidazole, has demonstrated the ability to inhibit both drug-sensitive and drug-resistant isolates of Mycobacterium tuberculosis in vitro with minimal inhibitory concentrations (MICs) ranging from 0.03 to 5.48 μg/ml. This compound targets gyrase B and has shown activity against intracellular and dormant bacteria in low-oxygen conditions, which is crucial for TB treatment.

In vivo studies in mice have shown that VXc-486 can significantly reduce mycobacterial loads in the lungs and has bactericidal effects. The compound has also exhibited inhibitory activity against multiple strains of other Mycobacterium species, including M. abscessus, M. avium complex, and M. kansasii, as well as Nocardia spp.

A phosphate prodrug form of VXc-486 has been found to be more potent in killing M. tuberculosis in vivo compared to the parent compound. When combined with other antimycobacterial drugs, the prodrug has the potential to sterilize M. tuberculosis infections, as demonstrated in a relapse infection study in mice. The prodrug's performance was at least as effective as moxifloxacin, a gyrase A inhibitor.

These results indicate that VXc-486 and its prodrug form are promising candidates for further development as treatments for both tuberculosis and nontuberculous mycobacterial infections, offering new hope for combating the growing issue of drug resistance in these diseases.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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