Core D In vitro Screening

摘要 微生物体外筛选(IVS)核心将提供全面的药敏试验 包括对五个项目的候选化合物的一系列分析。这些项目 代表发展的不同阶段，需要个别考虑。然而，a 贯穿所有5个项目的共同线索是全细胞筛查的要求。资源 IVS核心的专业知识包括巨噬细胞感染模型和细胞内敏感性， 浓度依赖杀灭与时间依赖杀灭、小菌落变体、抗生物膜 效力，血清漂移试验，静止期或“百日龄”培养，抗性 突变的产生和分析，以及药物组合分析。药物反应与 评估突变形成/预防和其他高级分析也是可用的。化合物 纯度将与药物化学核心(核心B)一起确认。数据 符合性和存储将使用协作药物发现公司进行处理和共享。 软件程序(参见数据共享)。Screen Core收藏的生物包括 28种病原体。康奈尔博士和巴里·克赖斯威思博士的实验室 (PHRI)提供广泛的临床菌株集合，具有良好的抗生素耐药性特征， 与纽约/新泽西州的私立、公立和退伍军人医院合作组装 大都会地区，以及世界各地的医院，将在 定义阻力配置文件的项目。BSL2、BSL3和精选代理BSL3实验室 为安全使用这一广泛的菌株收集提供了保障。这支队伍集合起来进行 这些体外分析在细菌药物发现和治疗方面有超过65年的经验。 抗生素敏感性及耐药性分析。集团的中等吞吐量体验 高精度和快速周转是对总体的重大和必不可少的贡献 项目的成功。 好了！

Abstract The microbial In Vitro Screening (IVS) Core will provide comprehensive susceptibility testing encompassing a range of assays for candidate compounds of the five projects. The projects represent various stages in development and require individual consideration. However, a common thread through all 5 projects is the requirement for whole cell screening. The resources and expertise of the IVS Core include macrophage infection model and intracellular susceptibility, concentration-dependent killing versus time-dependent killing, small colony variants, anti-biofilm efficacy, serum shift experiments, stationary phase or “one hundred day old” cultures, resistant mutant generation and analysis, and drug combination analysis. Drug response relationships to assess mutant formation/prevention and other advanced analysis are also available. Compound purity will be confirmed working in conjunction with the Medicinal Chemistry Core (Core B). Data conformity and storage will be handled and shared using the Collaborative Drug Discovery, Inc. software program (see Data Sharing). The organisms in the Screening Core’s collection include twenty-eight species of pathogens. The laboratories of Dr. Connell and Dr. Barry Kreiswirth (PHRI) provide extensive collections of clinical strains, well characterized for antibiotic resistance, assembled in collaboration with private, public and VA hospitals in the New York/New Jersey metropolitan area, as well as hospitals throughout the world, that will serve in later stages of the project to define resistance profiles. BSL2, BSL3 and Select Agent BSL3 laboratories are provided for the safe use of this extensive strain collection. The team assembled to carry out these in vitro assays has a combined experience of over 65 years in bacterial drug discovery and analysis of antibiotic susceptibility and resistance. The group's medium throughput experience with high precision and fast turnaround is a significant and essential contribution to the overall project’s success. !