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Feature Articles : Apr 15, 2008 ( )
Cell-Based Assay R&D Role Expands
Automation, Label-Free Tools, and Other Innovations Create Better Screening!--h2>
Cell-based assays have become a quick, lower-cost means of testing drug candidates for toxic effects in early discovery work. Informa Life Sciences’ upcoming “Cell-Based Assays” meeting will highlight some advances that are driving the field such as improved screening technologies, noninvasive monitoring, and the increasingly important incorporation of automation.
More than 50% of currently marketed drugs target GPCRs. The multitalented GPCRs affect a host of cellular processes that impact us from development to death. “GPCRs are the most validated class of druggable targets because of their involvement in critical metabolic and disease pathways as well as the success of such drugs on the market,” notes Helena Mancebo, Ph.D., president and CEO, of Multispan.
GPCR Drug Discovery
Multispan uses its technology to efficiently express active GPCRs in mammalian cells, reports Dr. Mancebo. “These complex proteins are typically difficult to express in cells and to purify in active states. This has created a bottleneck especially for generating antibodies against GPCRs.
DiscoveRx has developed a new family of cell-based assays for the detection of protein-protein interactions using an enzyme fragment complementation (EFC) assay. This system uses an enzyme acceptor (EA), an inactive alpha-galactosidase enzyme that binds to its enzyme donor (ED) forming an active enzyme that will hydrolyze a substrate and provide a signal. PathHunter™ a-Arrestin high-throughput screening assays monitor GPCR activation following ligand stimulation without the need for an imaging instrument, fluorescent protein tag, or radioactivity, points out Keith Olson, Ph.D., vp, R&D.
Screening Ion Channels
Ion channels play critical roles in processes that range from nervous-system signaling to muscle contraction and cell growth. Because of their global expression and importance they are sought after therapeutic targets.
Label-free detection technologies are becoming increasingly popular because they permit the noninvasive monitoring of live cells in real time. “We use cell-sensor impedance technology as a label-free means to monitor live cells,” reports Anker Jon Hansen, Ph.D., principal scientist at Novo Nordisk. “Measuring electrical impedance is a relatively new method to gauge cell-adhesive properties.”
Advances in Automation
The process of performing cell-based assays involves plating cells, equilibrating them to culture conditions, adding the compounds, performing the assay, and finally reading the results. This can be a slow and expensive process that produces variable results especially when done manually, according to Ali Griffen, Ph.D., associate team leader, cancer bioscience at AstraZeneca.
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