Formation of PROTAC ternary complexes measured with mass photometry

Small molecule-induced selective degradation of target proteins is one of the most promising new generation drug discovery approaches. Small bifunctional molecules, exemplified by PROTACs (PROteolysis-TArgeting Chimeras), can induce the recruitment of a target protein to an E3 ligase, subsequently forming a target/PROTAC/ligase ternary complex to facilitate the cellular target’s degradation via the proteasome. In this application note, Refeyn presents a mass photometry-based assay, which can inform on the aspects of the ternary complex formation.