HIGH-THROUGHPUT SCREENING

高通量筛选

基本信息

批准号：
8243721
负责人：
HAKIM DJABALLAH
金额：
$ 62.97万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8243721
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 Ensure Environment Equipment and supply inventories Explosion Gene Combinations Genes Genome Genomics Growth Homeostasis In Vitro Incubators Individual Institution Intervention Investigation Libraries Liquid substance Maintenance Malignant Neoplasms Memorial Sloan-Kettering Cancer Center Methods Mission Molecular Names Pathway interactions Pharmaceutical Chemistry Pharmaceutical Preparations Physiological Plants Play Positioning Attribute 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 complex biological systems 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

项目摘要

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鉴定生物活性化学物质来自图书馆的支架含有数千种离散化学物质，并且可能含有天然物质从植物等天然来源获得的物质。 MSKCC 已实施创建最先进的高通量筛选核心设施，配备现代机器人技术、定制筛选数据用于存储和查询数据以及建立供应战略合作的管理数据库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，配备板库、细胞分析培养箱、散装液体分配器 (Multidrops)、384/1536 液体处理器 (Apricot Designs TPS)、Perkin Elmer MicroBeta 计数器、两台 Perkin Elmer Victors 多重检测板读取器、两台 Molecular Device 吸光度扫描仪，以及一台 Amersham 多重检测成像仪。筛选数据采集和管理是通过定制软件 ORIS，由化学品注册和库存功能组成与自动数据加载器一起用于采集、分析和屏幕数据发布。该化合物库将增至多达 500,000 种来自选定商业供应商的离散化学品，并且还将包含各种各样的天然产物，一些是纯化的，另一些是提取物混合物，有待筛选和去重复识别和纯化活性产品。这种基础设施对持续的影响癌症研究将集中在以下领域： 1）化学癌症生物学以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（包括控制连接）的机制， 2）用作体内生化和代谢研究的放射性示踪剂的新型化学支架和使用癌症诊断，以及 3) 经典的药物发现过程，其中体外和/或基于细胞的目标进行筛选，并对所得的化学命中物进行二次和高内涵筛选，以便进一步优化其化学结构和药物特性，并显示出一定的抗病毒功效特定癌症的副作用很少或没有，使它们成为临床的良好候选药物。