BTZ043

BTZ043 (CAS No.: 1161233-85-7) is a benzothiazinone-class small molecule antibiotic with potent antimycobacterial activity, primarily investigated in tuberculosis drug discovery for its ability to target decaprenyl-phosphoribose epimerase (DprE1), a key enzyme in the biosynthesis of the mycobacterial cell wall arabinan. By covalently inhibiting DprE1, which functions in concert with DprE2 to catalyze the conversion of decaprenylphosphoryl ribose to decaprenylphosphoryl arabinose, BTZ043 disrupts cell wall assembly and leads to rapid bactericidal effects against Mycobacterium tuberculosis. The compound exhibits high potency in vitro, with minimal inhibitory concentrations in the low nanomolar range against M. tuberculosis H37Rv and related mycobacterial species, and demonstrates activity in infected macrophage models, indicating intracellular efficacy. BTZ043 also shows synergistic effects when combined with other antitubercular agents such as bedaquiline, enhancing bactericidal outcomes compared to monotherapy. In preclinical studies using murine models of chronic tuberculosis infection, oral administration over several weeks significantly reduces bacterial burden in lung and spleen tissues, supporting its utility as a lead compound for combination therapy development. BTZ043 is widely used as a chemical probe to study mycobacterial cell wall biosynthesis and to evaluate novel therapeutic regimens, with experimental concentrations or dosing regimens typically optimized based on specific assay systems and research objectives.