泛素
泛素蛋白连接酶类
计算生物学
药物开发
药物发现
泛素连接酶
蛋白质降解
小分子
药品
化学
生物
生物信息学
细胞生物学
生物化学
药理学
基因
作者
Rafael Maciel Ioris,Katherine Ferris,Vincenzo D'Angiolella
标识
DOI:10.1002/9783527836208.ch3
摘要
Many essential biological processes are regulated through protein–protein interactions. Some natural and synthetic small-molecule compounds also operate through induced protein proximity. In particular, molecular glue degraders are small drug-like compounds that prompt or strengthen the dimerization between E3 ubiquitin ligases and target proteins, prompting the target ubiquitination and subsequent proteasomal degradation. This and other pharmacological strategies of targeted protein degradation hold the promise to overcome some limitations of traditional occupancy-based therapeutic modalities. In this chapter, we summarize our current understanding of protein destabilization by molecular glue degraders, with a special focus on the following: (i) the serendipitous discoveries of some clinical and preclinical compounds and (ii) the first examples of intentional discoveries. By inducing proximity to E3 ligases, molecular glue degraders open up an exciting avenue for the development of novel therapeutics against otherwise undruggable proteins.
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