Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2

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• 作者：Sharad K. Verma ; Xinrong Tian ; Louis V. LaFrance ; C茅line Duquenne ; Dominic P. Suarez ; Kenneth A. Newlander ; Stuart P. Romeril ; Joelle L. Burgess ; Seth W. Grant ; James A. Brackley ; Alan P. Graves ; Daryl A. Scherzer ; Art Shu ; Christine Thompson ; Heidi M. Ott ; Glenn S. Van Aller ; Carl A. Machutta ; Elsie Diaz ; Yong Jiang ; Neil W. Johnson ; Steven D. Knight ; Ryan G. Kruger ; Michael T. McCabe ; Dashyant Dhanak ; Peter J. Tummino ; Caretha L. Creasy ; William H. Miller
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：December 13, 2012
• 年：2012
• 卷：3
• 期：12
• 页码：1091-1096
• 全文大小：360K
• 年卷期：v.3,no.12(December 13, 2012)
• ISSN：1948-5875

文摘

The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.

Keywords:

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