Dr. Stephan Kirchmaier, Promega, Walldorf
Confirming that a compound binds its intended target within living cells is essential for successful drug discovery yet remains technically challenging for novel or poorly characterized proteins. Traditional methods present significant limitations: biochemical thermal shift assays require purified proteins and lack cellular context. Live-cell tracer-based target engagement assays deliver excellent quantitative data but require known ligands for assay development—a significant barrier when pursuing first-in-class programs against targets lacking suitable tool compounds.
We present a novel live-cell target engagement platform that enables quantitative assessment of compound–target binding without requiring known ligands or purified proteins.
Validation across more than 20 target classes demonstrates broad applicability spanning diverse cellular compartments and protein families, including historically challenging targets. The streamlined workflow is fully compatible with high-throughput screening formats. This platform empowers discovery teams to identify and validate hits against novel targets earlier in the pipeline, generate reliable cellular potency data for medicinal chemistry optimization, and build confidence in target engagement before committing to downstream studies.