From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9 (Cell Chemical Biology)

Petrilli et al. describe the identification of high-affinity small-molecule binders to PCSK9 through two complementary hit-to-lead approaches. The lead compound was shown to bind to PCSK9 in a cellular thermal shift assay and subsequently developed into a targeted protein degrader.