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

双功能和分子胶正在成为解决具有挑战性的药物靶点的强大模式，但目前还没有普遍适用的发现策略。该项目将建立和开发一个基于十亿成员编码的效应子融合库的新型通用筛选平台，以鉴定可以将特定感兴趣蛋白招募到任何所需内源性细胞效应子系统的化合物。通过从头诱导效应物-靶蛋白复合物，化合物将触发蛋白质功能的催化和多功能调节，例如通过诱导或去除特定的PTM，或通过重新连接蛋白质运输或信号传导复合物，对化学探针发现和未来治疗产生深远影响。

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.