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

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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.