InCELL Hunter™: A Novel Cellular Assay Platform for the Direct Measurement of Compound Binding to Intracellular Targets in Intact Mammalian Cells

Version:: V1
File Name/Number:: 2013 SLAS
Year:: 2013

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Assays that directly detect compound binding inside cells can be of great utility in translating in vitro data to more biologically relevant models. However, these types of intracellular binding assays have not been possible so far. Cellular assays for these targets are limited to downstream activity-based readouts which can be difficult to develop, may not be proximal to the target, or may require reagents or knowledge that does not currently exist. Here, we describe the development of a novel cell-based assay for the detection of compound binding to intracellular proteins termed InCELL Hunter™. This assay bypasses the need for knowledge of downstream substrates or catalytic activity of the target, relieving many of the constraints of current cell-based assay technologies. We show the generic application of this technology to a number of challenging target classes including methyltransferases, bromodomains, and kinases. As demonstrated here, the assay reports cellular permeability and appropriately reports compound binding activity making this a promising platform for bridging the gap between in vitro assays and functional cellular assays.