Identification of potent, selective, cell-active inhibitors of the histone lysine methyltransferase EZH2

SK Verma, X Tian, LV LaFrance… - ACS medicinal …, 2012 - ACS Publications
SK Verma, X Tian, LV LaFrance, C Duquenne, DP Suarez, KA Newlander, SP Romeril…
ACS medicinal chemistry letters, 2012ACS Publications
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.
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.
ACS Publications