Science Spotlight: Chinese researchers advance PROTAC design

Two Chinese groups advanced the modular design of proteolysis-targeting chimera (PROTAC) using nanotechnology chemistry to fix core degrader liabilities. Both teams are from Peking University and degraded BRD4 as a proof of concept.

The Nature Communications paper authors focused on improving formulation and PK properties, building “split-and-mix” PROTACs on self-assembling polylactic acid (PLA)–PEG nanoparticles. They attached the target ligand and E3 ligase ligand separately to the polymer so that the functional degrader forms by co-assembly rather than as one large small molecule. The result was PROTAC molecules that functioned at lower doses for longer durations. ...