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Interest Group homepage at https://www.lab-robotics.org Presentation: HTS and Lead Optimization Using FLIPR
Joseph Gunnet, Ph.D.
Principal Scientist, Endocrine Therapeutics
The R.W. Johnson Pharmaceutical Research Institute, Rt. 202, Raritan, NJ 08869
The identification of functional agonists and antagonists for some G-protein coupled receptors (GPCRs) can be done by monitoring intracellular calcium mobilization. FLIPR (Fluorometric Imaging Plate Reader; Molecular Devices Corp.) allows GPCR-induced calcium responses to be accurately and reliably quantitated in an entire 96 well plate. With its CCD camera, FLIPR collects data at rate sufficient to follow the magnitude and time course of GPCR activation in each well. The large amount of information gathered from each well may be analyzed to simply identify hits in HTS or may be analyzed in more detail to optimize leads and ensure receptor-mediated activity. While most of the varibles in using FLIPR are the same as for any 96 well liquid handling system and fluorescent-based assay, performing HTS with FLIPR poses some unique issues and opportunities. We have worked through some of these biological, mechanical and data analysis issues and have successfully run HTS with FLIPR. Improvements in FLIPR hardware and data processing will soon be available and will expand the utility of an already useful instrument.
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Interest Group homepage at https://www.lab-robotics.org