Alan S Futran, Tao Lu, Katherine Amberg-Johnson, Jiayi Xu, Xiaoxiao Yang, Saidi He, Sarah Boyce, Jeffrey A Bell, Robert Pelletier, Takao Suzuki, Xianhai Huang, Heng Qian, Liping Fang, Li Xing, Zhaowu Xu, Stephen E Kurtz, Jeffrey W Tyner, Wayne Tang, Tao Guo, Karen Akinsanya, David Madge, Kristian K Jensen
The USP7 deubiquitinase regulates proteins involved in the cell cycle, DNA repair, and epigenetics and has been implicated in cancer progression. USP7 inhibition has been pursued for the development of anti-cancer therapies. Here, we describe the discovery of potent and specific USP7 inhibitors exemplified by FX1-5303. FX1-5303 was used as a chemical probe to study the USP7-mediated regulation of p53 signaling in cells. It demonstrates mechanistic differences compared to MDM2 antagonists, a related class of anti-tumor agents that act along the same pathway...
May 17, 2024: IScience