CORE 2: BIOCHEMICAL ASSAY CORE (MAILMAN)

生化分析核心： A.具体目标 1.目标1.使用现有的分析方法对由 可能感兴趣的研究项目或团队研究人员。 这一核心的主要目标是提供新型配体和典型化合物的功能图谱。 这包括一些目前批准的临床药物，来自文献的有趣的实验配体，以及 从项目研究项目中确定的或由外部来源建议的化合物。目前有几个 介绍一系列可区分典型激动剂和功能选择性激动剂的生化功能分析 配基。要将一种化验纳入这个核心，它必须是“常规的”，也就是说，一种稳健可靠的化验 这已经得到了项目科学家或外部合作者的验证。 我们之前的研究表明，一组独立的或主要的信号分析 相互独立将区分具有功能选择性特性的药物，并允许选择 具有新奇性质的试剂。我们认为，这种信号效应模式的差异不仅会 将配体相互区分，但也将预测临床前行为，并可能， 临床差异。因此，这一核心将精选额外的化合物输入到两个行为项目中 惠氏和杜克大学。 2.目标2：数据分析和检测改进。 为支持目标1，该核心还应具有几个辅助功能。首先，它将与Project一起工作 科学家寻找新的分析方法或细胞系(天然的或改良的)，以提高检测的灵敏度 功能选择性配体。其次，它将致力于提高以下方面的整体水平(牺牲量化) 大量使用的化验。第三，我们将尝试设计出易于使用的数据表示方法 药物学家用来研究功能选择性的。

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.