PBTZ169

PBTZ169 is a benzothiazinone derivative studied as an antitubercular agent. It inhibits DprE1, an essential enzyme in Mycobacterium tuberculosis involved in arabinogalactan biosynthesis, a key component of the cell wall. Activation by bacterial nitroreductases converts PBTZ169 into a reactive species that forms a covalent adduct with DprE1, resulting in inhibition of the enzyme and disruption of cell wall assembly. This mode of action gives PBTZ169 bactericidal activity against M. tuberculosis, including strains that are susceptible or resistant to first-line drugs in some settings.

In vitro assays have reported high potency of PBTZ169 against M. tuberculosis, and animal studies have demonstrated reductions in bacterial burden, with pharmacokinetic properties noted to be favorable relative to earlier benzothiazinone compounds. These attributes have supported progression into clinical development to assess safety, tolerability, and efficacy in humans.

Resistance to BTZ-class inhibitors can arise through mutations in the DprE1 enzyme or by decreased activation by nitroreductases, underscoring the importance of surveillance and combination strategies in clinical use. PBTZ169 is not approved for medical use and is primarily a research and development compound. It is one of several DprE1 inhibitors under investigation as part of an effort to expand the tuberculosis drug armamentarium, particularly for drug-resistant disease.