In the last few decades, the pharmaceutical industry has transformed people’s lives. However, the development of new drugs is becoming increasingly difficult and a paradigm shift in the drug discovery workflow is required to reduce attrition and transform conventional drug screening assays into translatable analytical techniques for the analysis of drugs in complex environments, both in-vitro and ex-vivo. The ability to visualize unlabelled compounds inside the cell at physiological dosages can offer valuable insight into the compound behavior both on and off-target.
SiLC-MS is a semi-automated methodology that allows the collection of intracellular contents using a modified CQ1 imaging system developed by Yokowaga. The instrument is equipped with a confocal microscope that allows bright field imaging as well as fluorescence imaging with 4 lasers (405, 488, 561, and 640 nm). Sampling is performed using the tips developed by Professor Masujima (1-4).
In this study, we show the applicability of the SiLC-MS technology to drug discovery, as it is crucial to identify compound and its metabolites when incubated in a mammalian cell at a therapeutic dose. We report on the validation studies performed using the SiLC-MS platform, in these validation studies we assess the ability to distinguish different cell types based on their metabolomic fingerprint, furthermore, we have also evaluated if this assay was sensitive enough to detect drugs intracellularly.
Presenter:
Carla Newman
Scientific Leader (Celluar Imaging and Dynamics), GSK
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