SideScout™

Understanding how small molecules interact with their protein targets and alter their conformational stability is key to uncovering molecular mechanisms of action. SideScout™ is a biophysical protein stability assay (similar to Thermal Proteome Profiling and related technologies) that addresses this question by quantitatively monitoring compound-induced protein stabilization or destabilization across the proteome. This approach enables proteome-wide target identification or deconvolution without the need for labels on the compound or target. By exposing native proteins to controlled solvent-induced denaturation in the presence or absence of compounds and monitoring changes in protein denaturation curves, our scientists can identify protein-ligand interactions in living cells or lysates under physiologically relevant conditions. This technique features high proteome coverage (up to 9,000 proteins) and can detect both compound-protein binding and protein complex formation, as for protein degraders and molecular glues. Concentration-resolved studies allow for affinity ranking (EC₅₀) of compounds and protein targets. SideScout™ provides an unbiased measure of drug-target engagement, identifies off-targets, and provides otherwise unattainable insights into a drug’s efficacy, selectivity, toxicity, and mechanism of action.

Various SideScout™ formats and readouts are available, including on-cell and in-lysate options, formats featuring area-under-the-curve compression, and readout options from western blot to quantitative proteomics.This technology is highly adaptable to diverse compound classes and biological matrices, supporting screening, target deconvolution, and validation studies.

SideScout™ is available as a kit to be performed at customer sites, with cutting-edge quantitative proteomic measurements and data analysis performed in our Freising location.