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Pretomanid (PA-824) is an experimental anti-tuberculosis compound and one of two nitroimidazoles in phase II clinical trials to treat tuberculosis. PA-824 was tested in vitro against a broad panel of multidrug-resistant clinical isolates and was found to be highly active against all isolates (MIC<1 microg/ml). The activity of PA-824 against M. tuberculosis was also assessed grown under conditions of oxygen depletion. PA-824 showed significant activity at 2, 10, and 50 microg/ml, similar to that of metronidazole, in a dose-dependent manner. PA-824 at 100 mg/kg in cyclodextrin/lecithin was as active as moxifloxacin at 100 mg/kg and isoniazid at 25 mg/kg and was slightly more active than rifampin at 20 mg/kg. Long-term treatment with PA-824 at 100 mg/kg in cyclodextrin/lecithin reduced the bacterial load below 500 CFU in the lungs and spleen. In mice, PA-824 has dose-dependent early bactericidal and sterilizing activity.
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Source | Braz J Med Biol Res (2017). Figure 1. PA-824 |
| Method | infection | |
| Cell Lines | CD4+ T cells | |
| Concentrations | 10 mg/kg | |
| Incubation Time | 20 day | |
| Results | These results suggested that PA-824 treatment decreased CD11a expressions on CD4+ T cells in lung and spleen and CS enhanced the efficacy of PA-824. |
| Molecular Weight | 359.26 |
| Formula | C14H12F3N3O5 |
| CAS Number | 187235-37-6 |
| Solubility (25°C) | DMSO 72 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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