Plug-and-play discovery of molecular glues: a new drug discovery paradigm

Bifunctionals and molecular glues are emerging as powerful modalities to address challenging drug targets, yet no generally applicable strategies for their discovery currently exist. This project will establish and develop a novel and universal screening platform based on billion-member encoded effector fusion libraries to identify compounds which can recruit a specific protein of interest to any desired endogenous cellular effector system. Through de novo induction of an effector-target protein complex, compounds will trigger catalytic and versatile modulation of protein function, for example by inducing or removing a specific PTM, or by rewiring protein trafficking or signalling complexes, with profound consequences for chemical probe discovery and future therapeutics.