The discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor

Qiangsheng Zhang; Xi Hu; Lu Li; Lidan Zhang; Guoquan Wan; Qiang Feng; Yongxia Zhu; Ningyu Wang; Zhihao Liu; Luoting Yu

doi:10.1039/d0cc04670a

The discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor

Chem Commun (Camb). 2021 Mar 25;57(24):3006-3009. doi: 10.1039/d0cc04670a. Epub 2021 Feb 24.

Authors

Qiangsheng Zhang¹, Xi Hu, Lu Li, Lidan Zhang, Guoquan Wan, Qiang Feng, Yongxia Zhu, Ningyu Wang, Zhihao Liu, Luoting Yu

Affiliation

¹ State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P. R. China. liuzhihao@scu.edu.cn yuluot@scu.edu.cn.

PMID: 33623946
DOI: 10.1039/d0cc04670a

Abstract

By targeting the unique Cys663 of EZH2, SKLB-0335 displays high paralog-selectivity on EZH2. Biochemical studies show that SKLB-0335 can covalently bind to EZH2 at its S-adenosylmethionine (SAM) pocket and inhibit H3K27Me3. SKLB-0335 could be an effective chemical probe with which to further investigate the specific biological functions of EZH2.