| Complex Signaling Pathway Analysis and Pharmacological Profiling via GPCRs using Cellular Dielectric Spectroscopy, A Novel Cellular Assay Technology |
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Presentation: 5C02 Session: Advanced Technology for Drug Discovery - Part 2Ryan McGuinness, Gordon Leung, Uma Oza, H. Roger Tang, Vivian Liu, Julia Michelotti, MDS Sciex Presenting Author: Ryan McGuinness, MDS Sciex - USA We present two independent studies focusing on three different GPCR targets utilizing Cellular Dielectric Spectroscopy (CDS) a novel label-free, functional, cell-based assay technology. The first study investigated the complex signal transduction of human MCHR1 expressed heterologously in CHO and U2-OS cells and endogenously in MOLT4 cells. The CDS platform uniquely enabled the dose-dependent differentiation of PTX-sensitive and Ca2+-coupled events simultaneously in the same microplate well and allowed pharmacological analysis of agonist and antagonist compounds. In the second study, CDS was used to perform hit confirmation for both agonists and antagonists with two different GPCR targets. Unique CDS response profiles of the hits were examined to identify non-silent antagonists and non-selective compounds. This allowed more focused pharmacological analyses of the most promising drug candidates. All results were compared to conventional secondary messenger assays. In summary, we simultaneously obtained information on signal transduction and ligand pharmacology without resorting to multiple (varied) assay-formats. |