CORE 2: BIOCHEMICAL ASSAY CORE (MAILMAN)

核心 2：生化检测核心（MAILMAN）

• 批准号: 8079094
• 负责人: Richard B Mailman
• 金额: $ 11.72万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8079094
• 关键词: Agonist; Behavioral; Biochemical; Biological Assay; Cell Line; Clinical; Data; Data Analyses; Goals; Hand; Ligands; Literature; Methods; Pattern; Pharmaceutical Preparations; Property; Research; Research Personnel; Research Project Grants; Scientist; Series; Signal Transduction; Source; Work; feeding; improved; interest; novel; pre-clinical

Biochemical Assay Core: A. SPECIFIC AIMS 1. Aim 1. Provide functional profiling using existing assays for compounds identified by the research projects or team researchers as being of potential interest. The primary goal of this core is to provide functional profiling of novel ligands and typical compounds. This includes some currently approved clinical drugs, interesting experimental ligands form the literature, and compounds identified from project research project, or suggested by external sources. There are currently in hand a series of biochemical functional assays that can distinguish typical agonists from functionally selective ligands. For an assay to be incorporated into this Core, it must be "routine," that is, a robust and reliable assay that has been validated by a project scientist or an external collaborator. Our previous research has shown that a battery of signaling assays that are independent or largely independent of each other will differentiate drugs with functionally selective properties, and allow selection of agents with novel properties. We believe that such differences in the pattern of signaling effects will not only differentiate the ligands from each other, but will also be predictive of preclinical behavioral and, possibly, clinical differences. Thus, this Core will feed select additional compounds into the two behavioral projects at Wyeth and at Duke. 2. Aim 2: Data analysis and assay improvement. In support of Aim 1, this Core shall also have several ancillary functions. First, it will work with Project scientists to look for new assays or cell lines (native or modified) that will enhance the sensitivity in detecting functionally selective ligands. Second, it will work to improve throughout (with sacrificing quantification) for assays that are heavily used. Third, we shall attempt to devise methods of data presentation that can be easily used by pharmacologists for studying functional selectivity.

生化测定核心： A.具体目标 1。AIM1。使用现有测定的功能分析 研究项目或团队研究人员是潜在感兴趣的。 该核心的主要目标是提供新型配体和典型化合物的功能分析。 这包括一些目前已批准的临床药物，有趣的实验配体构成文献，以及 从项目研究项目中确定的化合物，或由外部来源建议。目前有 将一系列可以区分典型激动剂与功能选择性区分的生化功能测定 配体。为了将测定纳入该核心，必须是“常规” 这已经由项目科学家或外部合作者验证。 我们以前的研究表明，一系列独立或很大的信号传导测定 彼此独立于功能选择性特性将药物区分开来，并允许选择 具有新特性的代理。我们认为，信号效应模式的这种差异不仅会 将配体彼此区分，但也将预测临床前行为，可能 临床差异。因此，该核心将为选择其他化合物送入两个行为项目 惠氏和杜克大学。 2。目标2：数据分析和测定改进。 为了支持AIM 1，该核心也应具有多个辅助功能。首先，它将与项目一起使用 科学家寻找新的测定法或细胞系（本机或修改），以增强检测的灵敏度 功能选择性配体。其次，它将有效地改进整个（牺牲量化） 大量使用的测定。第三，我们将尝试设计可以轻松的数据显示方法 药理学家用于研究功能选择性。