BTZ043 is an antibiotic with antimycobacterial activity. It targets mycobacterial cell wall synthesis by inhibiting DprE1, which, in conjunction with DprE2, catalyzes the epimerization of decaprenylphosphoryl ribose to decaprenylphosphoryl arabinose. BTZ043 is active against various Mycobacterium species in vitro, including M. smegmatis, M. bovis, and M. tuberculosis (MICs = 4, 2, and 1 ng/ml, respectively), as well as the actinobacterium N. brasiliensis (MIC50 = 0.125 μg/ml). It is also active against M. tuberculosis in RAW 264.7 murine macrophages (MIC = <10 ng/ml). BTZ043 (37.5 or 300 mg/kg for four weeks) reduces the number of viable M. tuberculosis cells in lung and spleen in a mouse model of chronic tuberculosis infection.
BTZ043 is a inhibitor of decaprenyl-phosphoribose-epimerase (DprE1), It can display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. in vitro: The inhibition of BTZ-resistant DprE1 followed the trend observed in the MIC measurements, with the C387G mutant being more resistant to inhibition by PyrBTZ01, PyrBTZ02, and BTZ043 (7- to 9-fold increases in IC50) than the C387S mutant (2.5- to 4-fold increases in IC50). in vivo: BTZ-043 were administered at 100 mg/kg twice daily by gavage, and sulfamethoxazole/trimethoprim (SXT), at 100 mg/kg sulfamethoxazole, was used as a positive control.