NanoBRET® to Quantify Live Cell Target Engagement at RAS and its Downstream Effectors

In this webinar, you will learn how:

  • NanoBRET® TE Assays broadly enable the quantitative determination of compound affinity/potency for specific targets inside cells
  • Protein-protein interactions and target protein activation states have a strong influence on drug compound pharmacology, using RAS-MAPK as an example
  • NanoBRET® TE Assays can be used to connect structural features of inhibitors to their biochemical properties in a cellular system


As a driver of tumorigenesis in numerous cell types, the RAS-MAPK pathway has been the subject of concerted drug discovery efforts for decades. Here we will present the use of NanoBRET® technology to quantify live cell target engagement (TE) to all described drug binding sites within the RAS-RAF-MEK-ERK pathway.

NanoBRET® TE is a well-established, real-time biophysical method for quantitative assessment of compound-target protein binding in live cells, without disruption of cellular membrane integrity. Specifically, cellular compound affinity, fractional occupancy, and residence time can be measured. Advantages of this method include the use of full-length target proteins in live cells in an addition-only, scalable, multi-well plate format.

Using the NanoBRET® TE method, we will show the impact of oncogenic KRAS (G12C) on engagement potency for downstream effectors, including BRAF. We have also developed a pan-KRAS NanoBRET® TE assay and will demonstrate detection of a variety of orthosteric and allosteric engagement mechanisms at this challenging target. Materials and methods to develop your own NanoBRET® TE assay are also available.



Matthew Robers, PhD
Senior Research Scientist and Group Leader, Target Engagement
Promega Corporation 

Matthew Robers is a Senior Research Scientist and Group Leader at Promega Corporation.  Matthew has authored over 25 peer-reviewed publications and published patents on the application of novel assay chemistries to measure intracellular protein dynamics. Matthew's team currently focuses on the development of new technologies to assess target engagement, and has developed a biophysical technique for quantifying compound affinity and residence time at selected targets within intact cells.

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