Pretomanid ((S)-PA 824) , a nitroimidazole, is used as an anti-tuberculosis drug for tuberculosis with MIC less than 2.8 μM.

MTB pan-sensitive and rifampin mono-resistant clinical isolates:0.015-0.25 ug/ml

体外实验显示，PA-824 对来自亚洲（印度和韩国）以及美国各地的多药耐药性临床分离株具有高效活性（MIC < 1 μg/ml），且对药敏感和多药耐药性的 M. tuberculosis 分离株同样具有活性（MIC 范围为 0.039 至 0.531 μg/ml）。[1] 最近的研究表明，PA-824 抗性基因（fgd1 [Rv0407] 和 ddn [Rv3547]）的单核苷酸多态性并不显著影响 PA-824 的 MIC 值（≤ 0.25 μg/ml）。[2]

在快速结核病鼠模型中，PA-824显示出显著的剂量依赖性抗微生物活性：在50 mg/kg的剂量下，PA-824在MC中能使肺部的CFU降低1个数量级以上；在100 mg/kg的剂量下，可使CFU降低约2个数量级，在300 mg/kg的剂量下，可降低3个数量级。此外，长期治疗（使用100 mg/kg的PA-824，配合环糊精/卵磷脂）也能够将肺部和脾脏中的细菌负荷降至500 CFU以下。[1] PA-824在结核病鼠模型中展现出时间依赖性的抗微生物活性，其最大观察到的杀菌效应为24天内每天0.1 log CFU。[3]

Isolated kinase assays: The intracellular kinase domains of human EGFR and erbB2 are cloned and expressed in the baculovirus/Sf21 system. The inhibitory activity of AZD8931 is determined with ATP at Km concentrations (0.4 mM for erbB2 and 2 mM for EGFR) using the ELISA method.

A method is used to determine the MICs by a microdilution plate assay by using M. tuberculosis H37Rv. INH is dissolved in sterile, double-distilled water at a stock concentration of 500 μg/ml. PA-824 is dissolved in 100% dimethyl sulfoxide (DMSO) to a stock concentration of 100 μg/ml. A 1:2 dilution series of both compounds is made in a separate 96-well microtiter plate by using the same diluents. The interior 60 wells of a 96-well round-bottom microtiter assay plate are seeded with 98 μl of bacterial suspension. Two microliters of each drug is transferred to the assay plate wells containing bacteria. The final concentrations of INH in the wells range from 10.0 to 0.039 μg/mL; the final concentrations of PA-824 range from 2.0 μg/mL to 8.0 pg/mL. The assay plates are incubated at 37 °C for at least 21 days and are observed every 3 to 4 days to evaluate changes in growth. Inhibition of growth is determined both by visual examination and with a spectrophotometer at an OD600.(Only for Reference)