BTZ043 Racemate 是一种癸二烯基磷酰-β-D-核糖 2'-差向异构酶 (DprE1) 抑制剂，用作新的抗分枝杆菌剂。

BTZ043 racemate is a decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1) inhibitor, used as a new antimycobacterial agent.

By targeting decaprenylphosphoryl-β-D-ribose 2'-epimerase, BTZ043 abolishes the formation of decaprenylphosphoryl arabinose, leading to cell lysis and death of Mycobacterium tuberculosis. BTZ043 displays similar activity against all clinical isolates of M. tuberculosis, including multidrug-resistant and extensively drug-resistant strains. BTZ043 displays significant activity against M. tuberculosis H37Rv and Mycobacterium smegmatis with MIC of 1 ng/mL (2.3 nM) and 4 ng/mL (9.2 nM), respectively, which is more potent than those of the existing tuberculosis (TB) drugs isoniazid (INH) and ethambutol (EMB) with MIC of 0.02-0.2 μg/mL and 1-5 μg/mL, respectively. BTZ043 is less effective in two different model systems (auxotrophy and starvation) involving metabolically inert M. tuberculosis, indicating that BTZ043 blocks a step in active metabolism similar to isoniazid (INH). BTZ043 treatment in M. smegmatis cells decreases the growth rate rapidly followed by a swelling of the poles and lysis of the cells after a few hours, which is similar but delayed in M. tuberculosis. [1] BTZ043 (1/4 MIC 0.375 ng/mL) in combination with TMC207 (1/4 MIC 20 ng/mL) has a stronger cidal effect on M. tuberculosis but not BTZ-resistant M. tuberculosis mutant than TMC207 alone at a concentration of 80 ng/mL. [2]

In a mouse model of chronic tuberculosis, administration of BTZ043 at 37.5 mg/kg or 300 mg/kg for 4 weeks reduces the bacterial burden in the lungs and spleens by 1 and 2 logs, respectively. [1]

957217-65-1

C17H16F3N3O5S

431.39

BTZ10526038;BTZ044;Benzothiazinone 10526038

H2O:<1 mgml
Ethanol:<1 mgml
DMSO:21 mg/mL (48.7 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years