Tb Drug Development

每年评估大约4,000至5,000种化合物对结核分枝杆菌的抗微生物生长抑制活性。 改进、标准化和采用新的分析方法来确定化合物对休眠(缓慢生长、持久或静止)的结核分枝杆菌生物体的活性。 每年评估大约1000种选定化合物抑制细胞内结核分枝杆菌复制。 在感染的哺乳动物细胞培养测试系统中评估治疗药物对结核分枝杆菌的疗效。该系统还必须为对照、未感染的哺乳动物细胞提供化合物细胞毒性的定量评估。 高通量开发和实施生物化学、靶向特异性结核分枝杆菌药物筛选试验 格式化 以高通量形式开发和实施结核分枝杆菌代谢阶段特异性药物筛选试验。 使用已公布的计算或神经网络方法，设计并实现一个用于预测药物特性的计算机系统，例如药物的溶解度、人体肠道吸收、生物利用度和潜在的抗结核药物毒性。

Evaluate approximately 4,000 to 5000 compounds per year for antimicrobial growth-inhibition activity against Mycobacterium tuberculosis. Improve, standardize, and adopt new assays for determining the activity of compounds against dormant (slowly growing, persistent, or quiescent) M. tuberculosis organisms. Evaluate approximately 1000 selected compounds per year for inhibition of replication of intracellular M. tuberculosis. Evaluate therapeutic agents for efficacy against M. tuberculosis in an infected mammalian cell culture test system. This system must also provide a quantitative assessment of cytotoxicity of compounds for control, uninfected mammalian cells. Develop and implement biochemical, target-specific Mycobacterium tuberculosis drug screening assays in a high-throughput Format Develop and implement M. tuberculosis metabolic stage-specific drug screening assays in a high-throughput format. Using published computational or neural network methods, design and implement an in silico system for predicting drug characteristics such as solubility, human intestinal absorption, bioavailability, and potential toxicities for therapeutic against against M. tuberculosis