CORE 2: BIOCHEMICAL ASSAY CORE (MAILMAN)

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.