CHARMED in Action

CHARMED is Sygnature’s pioneering platform for the discovery of bifunctional degraders, also known as PROTACs, innovatively combining plate-based chemistry with high-throughput biology. In this poster, we demonstrate the utility of the CHARMED platform for the rapid identification of degrader hits via ready-to-couple plates and our comprehensive hit-expansion toolbox.

As a clinically relevant oncology target in the Ras pathway, the phosphatase SHP2 was used as a model to demonstrate our capabilities in degrader synthesis and development of high-quality in vitro assays to rapidly profile compounds.

We here demonstrate the utility of CHARMED by application to a customer project, with rapid identification of active degraders with nanomolar potency. Screening potency data obtained using the HTRF assay were confirmed using an orthogonal method, i.e., Jess Simple Western, validating the robustness of the screening assay. 

In addition, we present our ongoing work on the next stages for CHARMED, including the generation of biophysics platforms for degrader characterization using SPR and fluorescence polarization.

The poster was presented at the Protein Degradation & Targeting Undruggables Congress in Basel on September 19th-20th 2023.