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BTZ043 Racemate (BTZ038, BTZ044) is a decaprenylphosphoryl-b-D-ribose 2-epimerase inhibitor. BTZ043 (BTZ038, BTZ044) is an enzyme which produces the cell wall of the pathogenic bacterium Mycobacterium tuberculosis. The MIC of BTZ043 racemate against M. tuberculosis H37Rv and Mycobacterium smegmatis were 1 ng/ml and 4 ng/ml, respectively.
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Source | Antimicrob Agents Chemother (2012). Figure 2. BTZ043 |
| Method | ||
| Cell Lines | M. tuberculosis H37Rv | |
| Concentrations | 0.375 ng/ml | |
| Incubation Time | 6 days | |
| Results | The data clearly show that under these conditions there is no longer any synergy between BTZ043 and TMC207, suggesting that inhibition of DprE1 is essential for the interaction. |
 |
Source | Antimicrob Agents Chemother (2012). Figure 1. BTZ043 |
| Method | resazurin checkerboard assay | |
| Cell Lines | M. tuberculosis H37Rv | |
| Concentrations | 0.375 ng/ml | |
| Incubation Time | 6 days | |
| Results | Compound interactions were evaluated by growing H37Rv in sub-MIC fractions of BTZ043 in combination with sub-MIC fractions of various front-line and experimental anti-TB compounds. |
| Cell Experiment | |
|---|---|
| Cell lines | macrophages infected with GFP-labeled M. tuberculosis |
| Preparation method | Intracellular activity of BTZ. Raw 264.7 macrophages (ATCC # TIB-71) (1.5 x 108 cells) were infected with H37Rv-GFP at an MOI of 1:1 in 300 ml of RPMI 1640 (Gibco) with 10% heat-inactivated fetal calf serum (Gibco) for 2 h at 37 °C with shaking (100 rpm). For each compound, a series of 16 two-fold dilutions in quadruplicate was tested. Infected cells were then incubated in the presence of the compound for 5 days at 37 °C, 5% CO2. Then, macrophages were stained with SYTO 60 (Invitrogen, S11342) followed by plate sealing and image acquisition. Confocal images were recorded on an automated fluorescent confocal microscope OperaTM (PerkinElmer) using a 20X-water objective (NA 0.70). Mycobacteria-GFP are detected using a 488-nm laser coupled with a 535/50 nm detection filter (green channel, GFP excitation) and cells labeled with Syto 60 are identified with 635-nm laser coupled with a 690/40 nm detection filter (red channel, Syto 60 excitation). |
| Concentrations | 0~1 μ M |
| Incubation time | 5 days |
| Animal Experiment | |
|---|---|
| Animal models | M. tuberculosis H37Rv infected BALB/c mice chronical model |
| Formulation | carboxymethyl cellulose formulation (0.25%) |
| Dosages | 37.5 or 300 mg/kg once daily, six times/week for four weeks |
| Administration | gavage |
| Molecular Weight | 431.39 |
| Formula | C17H16F3N3O5S |
| CAS Number | 957217-65-1 |
| Solubility (25°C) | DMSO 21 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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