HIGH-THROUGHPUT SCREENING

高通量筛选

• 批准号: 8375224
• 负责人: HAKIM DJABALLAH
• 金额: $ 31.62万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8375224
• 关键词: Address; Adverse effects; Apricot; Area; Biochemical; Biological; Biological Assay; Biological Factors; Biological Process; Biology; Cancer Biology; Cancer Center Support Grant; Cancer Diagnostics; Cells; Chemical Structure; Chemicals; Chemistry; Clinic; Collaborations; Computer software; Consultations; Core Facility; Custom; Data; Data Set; Databases; Detection; Development; Devices; Environment; Equipment and supply inventories; Explosion; Gene Combinations; Genes; Genome; Genomics; Growth; Homeostasis; In Vitro; Incubators; Individual; Institution; Intervention; Libraries; Liquid substance; Maintenance; Malignant Neoplasms; Memorial Sloan-Kettering Cancer Center; Methods; Mission; Molecular; Names; Pathway interactions; Pharmaceutical Chemistry; Pharmaceutical Preparations; Physiological; Plants; Play; Process; Property; Protein-Protein Interaction Map; Proteins; Publishing; RNA Interference; Reader; Regulation; Research; Research Infrastructure; Research Personnel; Robotics; Role; Scientist; Screening Result; Screening procedure; Secondary to; Small Interfering RNA; Source; Systems Biology; Technology; Training; Ursidae Family; Vendor; anticancer research; base; biological systems; cheminformatics; data acquisition; data management; design; drug candidate; drug discovery; functional genomics; genome sequencing; genome-wide; high throughput screening; in vivo; insight; interest; knockout gene; metabolic abnormality assessment; meter; novel; pre-clinical; programs; radiotracer; scaffold; small molecule; tool

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.

高通量筛选核心可以快速识别生物活性化学品 从含有数千种离散化学物质的库中提取支架， 从自然资源如植物中获得的。MSKCC已经实现了创建一个 最先进的高通量筛选核心设施，配备现代机器人，定制筛选数据 管理数据库，用于存储和查询数据，并为供应建立战略协作 化学品，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 六米线性轨道机器人平台，配有平板酒店、用于细胞分析的培养箱、散装液体 分配器（Multidrops），384/1536液体处理器（Apricot Designs TPS），Perkin Elmer MicroBeta计数器， 两个Perkin Elmer Victors多检测板读取器，两个Molecular Device吸光度扫描仪，以及 一台阿默舍姆多探测成像仪。筛选数据采集和管理通过 一个名为ORIS的定制软件，由化学品登记和库存功能组成 以及用于采集、分析和屏幕数据发布的自动数据加载器。的化合物 库将增长到500，000从选定的商业供应商离散化学品，还将包含 各种各样的天然产物，有些是纯化的，有些是提取物混合物，等待筛选和去复制 以鉴定和纯化活性产物。这种基础设施对正在进行的 癌症研究将在以下几个方面：1）化学癌症生物学，以发现新的控制 有助于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)用作体内生物化学和代谢研究的放射性示踪剂的新型化学支架及其用途 在癌症诊断中，以及3）经典的药物发现过程，其中体外和/或基于细胞的靶向 并对所得到的化学命中物进行二次和高含量筛选， 进一步优化其化学结构和药物性质，并显示出一定的抗肿瘤功效。 这些药物可以治疗特定的癌症，副作用很小或没有副作用，使其成为临床上良好的候选药物。