不依赖降解决定子的KAT2A招募扩展了CRBN分子胶的靶点空间

Samuel Ojeda1,2†, Meng Wang1,2†, Kheewoong Baek1,2, Wallace Bourgeois3, Alba Sommerschield3, Hong Yue1,2, Rebecca J. Metivier1,2, Panos Karagiannis1,2, Talya S. Levitz1,2, Yuan Xiong1,2, Katherine A. Donovan1,2, Scott A. Armstrong3, Eric S. Fischer1,2* Using small molecules to achieve targeted protein degradation (TPD) of disease- associated proteins is a powerful therapeutic approach to access otherwise unattainable pharmacology, with a growing number of molecules in clinical development (1, 2). Mechanistically, TPD in- volves hijacking the cellular ubiquitylation machinery by inducing proximity between an E3 ubiquitin ligase and the target protein of interest (POI) to facilitate POI polyubiquitylation and its subsequent proteasome- dependent degradation (3). …