Photo‐click Proteolysis‐Targeting Chimeras Enable Intracellular Generation of PROTACs for Precise Dual Protein Degradation

Proteolysis-targeting chimeras (PROTACs) are an emerging therapeutic modality via targeted protein degradation, but plagued by concerns about systemic toxicity and a poor pharmacokinetic profile. To tackle the issues, we have devised a photo-click proteolysis targeting chimera (PCPTAC) that enables spatiotemporally controllable intracellular synthesis of PROTACs by photo-triggered bioorthogonal ligation. A photocaged dibenzosilacycloheptyne (photo-DBSH) and the complementary azide were deployed