CORE 2: BIOCHEMICAL ASSAY CORE (MAILMAN)

生化试验核心： A.具体目标 1.目标1。使用现有的检测方法，为通过以下方法鉴定的化合物提供功能分析 研究项目或团队研究人员作为潜在的兴趣。 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。 这包括一些目前批准的临床药物，文献中有趣的实验配体， 从项目研究项目中确定的化合物，或外部来源建议的化合物。目前在 一系列的生化功能检测，可以区分典型的激动剂和功能选择性激动剂， 配体。对于要纳入本核心的检测，它必须是“常规”的，即稳健可靠的检测 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，一组独立或主要 彼此独立将区分具有功能选择性性质的药物，并允许选择 具有新特性的试剂。我们相信，这种信号效应模式的差异不仅会 将配体彼此区分，但也将预测临床前行为，并且可能， 临床差异。因此，这个核心将选择额外的化合物喂入两个行为项目， 惠氏和杜克大学。 2.目的2：数据分析和测定改进。 为支持目标1，该核心还应具有若干辅助功能。首先，它将与Project 科学家们寻找新的检测方法或细胞系（天然的或修饰的）， 功能选择性配体。第二，它将努力提高吞吐量（牺牲量化）， 被大量使用的分析。第三，我们将尝试设计数据呈现的方法， 药理学家用来研究功能选择性。

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.