HIGH-THROUGHPUT SCREENING

高通量筛选核心允许快速鉴定生物活性化学物质 来自图书馆的脚手架，含有数千种离散的化学物质，可能含有天然的 从植物等自然来源中获得的物质。MSKCC已经实现了创建一个 最先进的高通量筛查核心设施，采用现代机器人技术，定制筛查数据 管理数据库，用于存储和查询数据，并为供应商建立战略协作 并提供药物化学优化方面的专业知识。该设施包含一个定制的 六米直线轨道机器人平台，配备平板旅馆、细胞分析孵化器、散装液体 分配器(多滴)、384/1536液体处理机(Apricot设计TPS)、Perkin Elmer MicroBeta计数器、 两个Perkin Elmer Victors多检测平板读取器，两个分子器件吸光度扫描仪，以及 一台amersham多探测成像仪。筛选数据的采集和管理通过 名为Oris的定制软件，由化学品注册和库存功能组成 以及用于采集、分析和屏幕数据发布的自动数据加载器。该化合物 来自选定商业供应商的库将增长到最多500,000种离散化学品，还将包含 种类繁多的天然产物，一些是提纯的，另一些是萃取物混合物，等待筛选和去复制 对活性产物(S)进行鉴定和纯化。这样的基础设施对正在进行的 癌症研究将在以下方面进行：1)化学癌症生物学发现新的控制方法 帮助进一步阐明已知或发现新的癌症途径的机制，包括控制连接， 2)用作体内生化和代谢研究和使用的放射性示踪剂的新型化学支架 在癌症诊断中，以及3)在体外和/或基于细胞的靶点的经典药物发现过程 对得到的化学物质进行筛选，并对其进行二次筛选和高含量筛选 进一步优化它们的化学结构和药物性质，并显示出一定的抗炎效果 具有很小或没有副作用的特定癌症，使其成为临床上很好的候选药物。

The High-Throughput Screening Core allows the rapid identification of biologically active chemical scaffolds from libraries containing several thousand discrete chemicals, and potentially containing naturally occurring ones obtained from natural sources such as plants. MSKCC has implemented the creation of a state of the art high throughput screening core facility with modern robotics, custom built screening data management databases for storing and querying data, and setting up strategic collaborations for the supply chemicals and to provide expertise in medicinal chemistry optimization. The facility contains a custom built six meter linear track robotic platform equipped with plate hotels, incubators for cell based assays, bulk liquid dispensers (Multidrops), 384/1536 liquid handlers (Apricot Designs TPS), a Perkin Elmer MicroBeta counter, two Perkin Elmer Victors multi-detection plates readers, two Molecular Device absorbance scanners, and one Amersham Multi-detection imager. Screening data acquisition and management is handled through custom built software named ORIS, which is composed of a chemical registration and inventory function together with an automated data loader for acquisition, analysis and screen data publishing. The compound library will grow to up to 500,000 discrete chemicals from selected commercial vendors and will also contain a wide variety of natural products, some purified and others in extract mixtures pending screening and dereplication to identify and purify the active product(s). The impact of such an infrastructure on the ongoing cancer research will be in the following areas: 1) Chemical cancer biology to discover novel control mechanisms to help further elucidate known or discover novel cancer pathways including control junctions, 2) Novel chemical scaffolds for use as radiotracers for biochemical and metabolic studies in vivo and for use in cancer diagnostics, and 3) the classical drug discovery process in which in vitro and/or cell based targets are screened and the resulting chemical hits are subjected to secondary and high content screens, in order to further optimize their chemical structures and their drug properties, and to show some efficacy against the specific cancer with little or no side effects, making them good drug candidates for the clinic.