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

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.

Citation

Qiangsheng Zhang, Xi Hu, Lu Li, Lidan Zhang, Guoquan Wan, Qiang Feng, Yongxia Zhu, Ningyu Wang, Zhihao Liu, Luoting Yu. The discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor. Chemical communications (Cambridge, England). 2021 Mar 25;57(24):3006-3009

PMID: 33623946

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