Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones?
Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones?
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DOI：
10.1021/acs.jmedchem.7b01272
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发表时间：
2018-01-25
影响因子：
7.3
通讯作者：
Churcher, Ian
中科院分区：
文献类型：
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作者：
Churcher, Ian
靶向蛋白质降解，利用双功能小分子（Protacs）从细胞内去除特定蛋白质，已经成为一种新的药物发现策略，具有提供现有方法无法实现的治疗干预的潜力。在这个观点中，该领域的简史从药物发现的角度进行了调查，重点是知识的关键进展，这些进展导致了蛋白质降解概念的定义和例证，以及它们在药物发现中的应用。这种方法有可能给药物发现带来颠覆性的变化；讨论了该技术的许多潜在优势和面临的突出挑战。
Targeted protein degradation, using bifunctional small molecules (Protacs) to remove specific proteins from within cells, has emerged as a novel drug discovery strategy with the potential to offer therapeutic interventions not achievable with existing approaches. In this Perspective, the brief history of the field is surveyed from a drug discovery perspective with a focus on the key advances in knowledge which have led to the definition and exemplification of protein degradation concepts and their resulting applications to medicine discovery. The approach has the potential to bring disruptive change to drug discovery; the many potential advantages and outstanding challenges which lie ahead of this technology are discussed.