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Technology Seminar

Converging into focus: HTS, HCS and stem cells by Richard M. Eglen, Wednesday, March 11, 2009, 3:00 p.m., Seminar Room 6, LG/F, Laboratory Block, Li Ka Shing Faculty of Medicine -


Over the past decade, the use of cell-based assays has accelerated in modern drug discovery. Indeed, the majority of assays in either target validation or lead identification/optimization all employ cell-based systems. A very wide range of target classes can now be addressed by cell-based approaches including G protein coupled receptors (GPCRs), kinases (TKs, RTKs), nuclear hormone receptors (NHRs) and ion channels. One implicit assumption in these approaches is that the functional response provides a better definition of both the target physiology as well as its pharmacological interaction with novel compounds.

However, classical functional assays frequently use cell phenotypes that differ markedly from those found in human pathology. In particular, the reliance on the use of immortalized clonal cells, often optimized for the automation and detection systems in the HTS laboratory, raises concerns as to the clinical relevance of both the target validation studies as well as lead compounds selected for subsequent development. Consequently, some drug discovery programs are moving towards a broader adoption of primary and stem cells, as well as using sophisticated cell-based assays which employ high content analysis (HCA) and high content screening (HCS) techniques.

This presentation will discuss these emerging trends in drug discovery, with an emphasis on assays for a key drug discovery target classes, the GPCRs.


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