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

分子胶的即插即用发现：新的药物发现范例

• 批准号: 2753175
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2753175
• 关键词: Plug; play; discovery; molecular; glues

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.

双功能和分子胶正在成为解决具有挑战性的药物靶标的强大方法，但目前尚不存在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效应融合库的新型通用筛选平台，以识别可以招募任何所需内源细胞效应系统感兴趣的特定蛋白质的化合物。通过从头诱导效应子-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复合物，对化学探针的发现和未来的治疗产生深远的影响。