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bedaquiline + pretomanid + TBD09 is an experimental oral combination regimen being developed by the Bill & Melinda Gates Medical Research Institute for the treatment of pulmonary tuberculosis. This three-drug regimen combines two established anti-tuberculosis agents with a novel compound. Bedaquiline is a diarylquinoline that inhibits mycobacterial ATP synthase, an essential enzyme for energy production in *Mycobacterium tuberculosis*. Pretomanid is a nitroimidazole that acts by inhibiting mycolic acid biosynthesis (disrupting cell wall integrity) and by releasing nitric oxide, which acts as a respiratory poison under anaerobic conditions. TBD09 (also known as GSK3036656 or GSK656) is a novel benzoxaborole that inhibits leucyl-tRNA synthetase (LeuRS), thereby blocking protein synthesis. The combination is currently being evaluated in Phase 2 clinical trials to determine its safety, bactericidal activity, and potential to simplify or shorten treatment for drug-sensitive pulmonary tuberculosis.
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