Novel Anti-Tuberculosis Compounds
Keywords: Tuberculosis, macrophage, antibiotic
The resurgence of tuberculosis, caused primarily by Mycobacterium tuberculosis (Mtb), and the emergence of multidrug-resistant and extensively drug-resistant Mtb strains underscore the need for new drugs with alternative modes of action. The interaction between the mycobacterial thioredoxin reductase (TrxR) and its substrate thioredoxin (Trx) is a promising new drug target for the treatment of tuberculosis, since Mtb lacks the common glutathione system and the mycobacterial TrxR exhibits substantial differences in sequence, mechanism, and structure compared to human TrxRs. It has been shown that TrxR is essential for thiol redox homeostasis, and genetic inactivation in vivo eradicates Mtb during acute and chronic mouse infections (Lin et al., PLoS Pathog. 2016).
To further enhance the bioactivity of promising compounds, researchers at TU Dortmund University have focused on optimizing the physicochemical properties that are important for permeability, since M. tuberculosis has an unusually thick and impermeable cell wall.
Competitive Advantages
- A novel class of compounds that inhibit a novel target with the potential to overcome M. tuberculosis’s resistance to other drugs
- The viability of infected macrophages is not affected
- Increased bioactivity due to optimized permeability through the cell wall of M. tuberculosis
Commercial Opportunities
The technology is available for licensing and further therapeutic development.
Current Status
The researchers are preparing to advance the project toward studies in mice to confirm in vivo efficacy, as well as ADME-Tox studies. If you are interested, we would be happy to provide you with information regarding the patent status.
Relevant Publications
Koch, O., et al. (2013) Identification of M. tuberculosis thioredoxin reductase inhibitors based on high-throughput docking using constraints. J. Med. Chem. 56(12): 4849-59.
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An invention of TU Dortmund.
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