Assay development and screening for molecular targets and discovery

分子靶标和发现的测定开发和筛选

基本信息

批准号：
10702745
负责人：
Barry Okeefe
金额：
$ 221.76万
依托单位：
DIVISION OF BASIC SCIENCES - NCI
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/10702745
关键词：
Biochemical Biochemistry Biological Biological Assay Biology Cells Chemicals Chemistry Collaborations Communicable Diseases Component of the Center for Cancer Research Development Drug Modelings Evaluation Extramural Activities Future Information Technology Intramural Research Program Investments Laboratories Lead Libraries Malignant Neoplasms Molecular Biology Molecular Target NCI Center for Cancer Research Natural Products Natural Products Chemistry Output Pathway interactions Phenotype Plicamycin Pre-Clinical Model Principal Investigator Protein Chemistry Research Research Personnel Science Technology Therapeutic Transcriptional Regulation Translational Research United States National Institutes of Health Validation Work analog assay development base bioactive natural products cellular targeting clinical development cytotoxicity genomic platform high throughput screening immunoregulation programs repository screening translational applications translational potential uptake

项目摘要

Assay development efforts focus on the configuration, optimization and validation of high-throughput assays to screen pure compound libraries and natural product extracts for modulators of specific molecular and cellular targets and associated cellular phenotypes. The section also develops and applies assays to characterize active molecules in mechanism of action studies and to prioritize compounds for further advancement toward utilization as probes and therapeutics. Nine cell-based assays were developed (in addition to 4 biochemical assays developed in collaboration with the Protein Chemistry and Molecular Biology Section), 11 high-throughput screening (HTS) campaigns were performed and 12 assays were performed in support of natural products chemistry. Biological characterization studies were performed on numerous hits from completed HTS campaigns, including utilization of a chemical genomics platform to assess mechanisms of action of natural product modulators of transcriptional regulation and cytotoxicity. Natural products-focused HTS has also led to development of lead compounds being further assessed in pre-clinical models of drug uptake, immunoregulation, transcriptional regulation, as well as clinical development of mithramycin and analogs.

测定开发工作的重点是针对特定分子和细胞靶标的调节剂以及相关的细胞表型的调节剂筛选纯复合库的配置，优化和验证。本节还开发并应用测定法以表征作用研究机理中的主动分子，并优先考虑化合物，以进一步发展作为探针和治疗剂的利用。开发了9种基于细胞的测定（除了与蛋白质化学和分子生物学部分合作开发的4种生物化学测定外，还进行了11项高通量筛选（HTS）运动，并进行了12种测定，以支持天然产物化学。生物表征研究对完成的HTS运动的众多命中进行了研究，包括利用化学基因组学平台来评估转录调节和细胞毒性的天然产物调节剂的作用机理。以天然产品为中心的HTS还导致了铅化合物的发展，并在药物摄取，免疫调节，转录调控以及毛金霉素和类似物的临床发展中进一步评估了铅化合物。