Chemical Library Screening

化学库筛选

基本信息

批准号：
9149761
负责人：
MARK MERCOLA
金额：
$ 30.08万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-05-01 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9149761
关键词：
Advanced Development Animal Disease Models Applications Grants Area Automation Award Basic Science Biochemical Biochemical Process Biological Assay Biology Budgets Cancer Center Cancer Center Support Grant Cell model Cell physiology Cells Chemicals Collection Communication Computers and Advanced Instrumentation Consult Consultations Core Facility Crystallography Data Data Analyses Detection Development Doctor of Philosophy Drug Kinetics Equipment Experimental Designs Faculty Feedback Funding Funding Mechanisms Generations Genomics Grant Image Institutes Investments Laboratories Lead Leadership Libraries Life Maintenance Malignant Neoplasms Microscopy Miniaturization Natural Products Pathogenesis Pharmaceutical Chemistry Pharmaceutical Preparations Production Property Publications Research Research Infrastructure Research Personnel Resource Sharing Resources Science Scientist Screening for cancer Services Staging Structure-Activity Relationship Surveys Technology Testing Time Translating Translational Research Tumor Biology United States National Institutes of Health Validation Work abstracting analog assay development base cellular targeting combinatorial chemistry cost drug development drug discovery follow-up high throughput screening in vivo induced pluripotent stem cell insight meetings member novel physical property programs scale up screening small molecule small molecule libraries structural biology three dimensional cell culture tumor validation studies

项目摘要

5.7 Abstract - CHEMICAL LIBRARY SCREENING (Core Group B) The Chemical Library Screening Shared Resource (CLS) (Core Group B) offers Cancer Center scientists the ability to develop and conduct small- and large-scale chemical library screens and perform hit optimization and validation for the generation of selective probes of biochemical and cellular processes of tumor biology. This resource, located within the large Conrad Prebys Center for Chemical Genomics at SBMRI (a national Comprehensive Center for both the NIH MLPCN and NCI CBC programs), provides Cancer Center faculty with access to technology, expertise and infrastructure resources to develop novel means for characterizing cellular targets involved in tumor pathogenesis and tumor onset and to advance the development of new lead molecules for anti-tumor therapies. CLS consists of four specialized but highly integrated facilities: 1) the High Throughput (HT) Assay Development Facility provides technical and scientific support in the development, miniaturization, and implementation of cell-based and biochemical HT assays, assists with characterization of compounds identified in primary screens through development and execution of secondary and orthogonal assays, as well as performs structure-activity-relationship, selectivity-panel and mechanism-of-action studies; 2) the Compound Management and HT Screening Facility manages the Institute's natural product and small molecule chemical compound libraries (over 700,000 compounds), maintains automation and detection equipment, and executes large-scale screening campaigns; 3) the High Content Screening Facility supports all aspects of development, execution, and image-data analysis of image-based high content screens, as well as aids with high-throughput microscopy assays for non-screening applications; and 4) the Medicinal Chemistry Facility provides technical support and expertise in the areas of medicinal chemistry, combinatorial chemistry, scale-up for advanced studies, and determination of physical properties. Over the past 5 years, a total of 36 Cancer Center members used the services of the CLS Shared Resource, carrying out 26 successful Cancer Center chemical biology projects, 12 advancing to hit-to-lead optimization, and 7 successfully generated leads with sufficient potency and drug-like properties to be explored in vivo animal models of disease. This direct access to experts and technology in chemical biology and early-stage drug development for CLS has provided consultation and technical sections for 57 grant proposals submitted by Sanford-Burnham Cancer Center PIs, of which 26 were awarded. CLS staff has been included in 44 Cancer Center member publications as co- authors, reflecting their important contribution to these scientific discoveries. In addition, data produced by CLS, access to chemical libraries and advanced instrumentation, consulting, and other services, contributed to at least 37 additional publications. The CCSG funding (10% of the total CLS budget), leverages substantial institutional investment in this extensive drug discovery infrastructure, and provides Cancer Center researchers with priority access to this technology strongly supporting both discovery and early translational research.

5.7 摘要 - 化学库筛选（核心组 B）化学图书馆筛选共享资源 (CLS)（核心组 B）为癌症中心科学家提供开发和进行小型和大规模化学库筛选以及执行命中优化的能力以及验证肿瘤生物学生化和细胞过程的选择性探针的生成。该资源位于 SBMRI 的大型康拉德普雷比斯化学基因组学中心（国家级 NIH MLPCN 和 NCI CBC 项目的综合中心）为癌症中心的教职员工提供获得技术、专业知识和基础设施资源，开发表征细胞的新方法参与肿瘤发病机制和肿瘤发生的靶点，并推进新先导药物的开发用于抗肿瘤治疗的分子。 CLS 由四个专业但高度集成的设施组成：1) High 通量 (HT) 检测开发设施为开发提供技术和科学支持，小型化以及基于细胞和生化 HT 测定的实施有助于表征通过开发和执行二次和正交筛选在初级筛选中鉴定出的化合物分析，以及进行结构-活性关系、选择性面板和作用机制研究； 2) 化合物管理和 HT 筛选设施管理研究所的天然产品和小化合物分子化合物库（超过 700,000 种化合物），保持自动化和检测设备，并开展大规模筛查活动； 3) 高内涵筛选设施支持所有基于图像的高内容屏幕的开发、执行和图像数据分析方面，以及有助于非筛选应用的高通量显微镜检测； 4）药物化学该设施提供药物化学、组合化学、用于高级研究的放大和物理特性的测定。过去5年，共36 癌症中心成员使用 CLS 共享资源的服务，成功开展了 26 项癌症治疗中心化学生物学项目，12 个进展至先导化合物优化，7 个成功生成先导化合物具有足够的效力和类似药物的特性，可以在疾病动物模型的体内进行探索。这个直接为 CLS 提供了接触化学生物学和早期药物开发方面的专家和技术的机会桑福德伯纳姆癌症中心 PI 提交的 57 项资助提案的咨询和技术部分，其中26人获奖。 CLS 工作人员已被纳入 44 个癌症中心成员出版物中，作为共同作者，反映了他们对这些科学发现的重要贡献。此外，产生的数据 CLS、化学图书馆和先进仪器、咨询和其他服务的访问，有助于至少还有 37 份出版物。 CCSG 资金（占 CLS 预算总额的 10%）利用了大量资金对这一广泛的药物发现基础设施的机构投资，并为癌症中心的研究人员提供优先获得该技术，有力支持发现和早期转化研究。