High Throughput Screening Shared Resource

高通量筛选共享资源

基本信息

批准号：
9097628
负责人：
JAMES K. WILLSON
金额：
$ 15.25万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
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/9097628
关键词：
Applications Grants Basic Science Biochemical Biochemistry Bioinformatics Biological Assay Biological Markers Cancer Biology Cancer Center Cancer Center Support Grant Cells Chemicals Chemistry Clinical Core Facility Data Analyses Data Collection Data Storage and Retrieval Development Dose Drug Targeting Excretory function Faculty Financial Support Foundations Fractionation Funding Genes Genomic Library Goals Information Resources Management Journals Laboratories Lead Legal patent Libraries Licensing Literature Malignant Neoplasms Management Information Systems Measures Medical center Metabolism Natural Products Pathway interactions Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacology Positioning Attribute Preclinical Drug Development Principal Investigator Proteins Publications RNA Interference RNA interference screen Research Research Infrastructure Resource Sharing Resources Retrieval Scientific Advances and Accomplishments Screening Result Small Interfering RNA Structure Structure-Activity Relationship Sum Technical Expertise Technology Therapeutic Human Experimentation Therapeutic Intervention Toxic effect Training Translational Research Ursidae Family Work absorption abstracting analog assay development base cancer therapy cheminformatics collaborative environment data integration data management drug discovery experience follow-up genome-wide genome-wide analysis high throughput screening in vivo instrumentation member novel novel therapeutics pre-clinical programs response screening small molecule small molecule libraries square foot success therapeutic protein

项目摘要

Harold C. Simmons Cancer Center High Throughput Screening Shared Resource (Translational Research Resource) Project Summary/Abstract The High Throughput Screening Shared Resource has a strong track record in both chemical and RNAi screening. The former is carried out via full-file and subset screening of our compound library (+230,000 compounds) and by supporting confirmation, dose-response studies, and secondary activity profiling of selected hit compounds as well as synthesized and purchased synthetic analogs. For early, preclinical drug discovery efforts, the Resource provides advanced project support that encompasses structure-activity relationship (SAR) studies, bioassay-guided fractionation of natural products, cheminformatics and bioinformatics support, and data storage and integration via our Laboratory Information Management System (LIMS). For the identification of novel therapeutic protein targets and pathways, the Core carries out screening of genome-wide siRNA libraries and supports confirmation and characterization of the genes and pathways identified as potential points of therapeutic intervention. All of these activities are engaged in ~3900 square feet of laboratory space using the latest in screening technologies and instrumentation by a director who has several years experience in industrial and academic drug discovery and a well trained and experienced scientific staff. Together, the director and scientific staff bring more than 30 years of experience to bear on every screening project. The Resource works collaboratively with principal investigators (biologists, chemists, and statisticians) and other shared resource and core facilities to achieve both therapeutic and basic research goals. The success and impact of the Resource can also be measured in terms of the pre-clinical drug and target discovery activities that are enabled downstream of screening. To date, the Resource has executed over 195 screening projects (98 small molecule and 97 RNAi screens). From these efforts, over 64 publications derived from high throughput screening have appeared in high profile journals and the patent literature. These results have provided the foundation for successful funding of over 60 grant applications for screening programs and advanced characterization of established chemical leads and drug targets. Importantly, several discoveries from screening programs have led to commercial follow up via licensing. One of the keys to our success as a collaborative core facility has been the tight integration of our expertise with medicinal chemistry, ADME (Absorption, Distribution, Metabolism, and Excretion), and in vivo efficacy. Seven (7) chemistry faculty members in the Biochemistry Department enable lead optimization and development in pre-clinical drug discovery programs. Their efforts are supported and enhanced by the Pharmacology Core which carries out ADME, toxicity, and efficacy studies. In sum, the multidiscipline and collaborative environment of pre-clinical drug and target discovery is effectively and productively integrated with cutting edge research in cancer biology by Simmons Cancer Center members.

哈罗德·西蒙斯癌症中心高通量筛选共享资源（转化研究资源）项目概要/摘要高通量筛选共享资源在化学和 RNAi 方面拥有良好的记录筛选。前者是通过我们的化合物库（+230,000 化合物）并通过支持确认、剂量反应研究和次级活性分析选择热门化合物以及合成和购买合成类似物。对于早期、临床前药物发现工作，该资源提供了包含结构活动的高级项目支持关系（SAR）研究、生物测定引导的天然产物分馏、化学信息学和通过我们的实验室信息管理系统提供生物信息学支持、数据存储和集成（实验室信息管理系统）。为了鉴定新的治疗蛋白靶点和途径，核心进行筛选全基因组 siRNA 文库并支持基因和通路的确认和表征被确定为潜在的治疗干预点。所有这些活动都在~3900平方米的范围内进行英尺的实验室空间，由一位拥有丰富经验的主任使用最新的筛选技术和仪器多年的工业和学术药物发现经验以及训练有素、经验丰富的团队科学人员。主任和科研人员共同带来 30 多年的经验每个筛选项目。该资源与主要研究人员（生物学家、化学家和统计学家）合作，其他共享资源和核心设施，以实现治疗和基础研究目标。成功资源的影响也可以通过临床前药物和靶点发现来衡量筛选下游启用的活动。迄今为止，该资源已执行超过 195 次筛选项目（98 个小分子和 97 个 RNAi 筛选）。通过这些努力，超过 64 篇出版物来自高水平通量筛选已出现在知名期刊和专利文献中。这些结果有为 60 多项筛选项目资助申请的成功资助奠定了基础已建立的化学先导物和药物靶标的高级表征。重要的是，有几个发现筛选计划已导致通过许可进行商业后续行动。作为我们成功的关键之一协作核心设施将我们的专业知识与药物化学、ADME 紧密结合（吸收、分布、代谢和排泄）和体内功效。七 (7) 名化学教师生物化学部门的成员致力于临床前药物的先导化合物优化和开发发现计划。他们的努力得到了药理学核心的支持和加强，该核心进行 ADME、毒性和功效研究。总之，临床前的多学科协作环境药物和靶点发现与癌症生物学的前沿研究有效且富有成效地结合起来由西蒙斯癌症中心成员撰写。