Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2.
Journal: ACS Medicinal Chemistry Letters
Published:
Abstract
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.
Authors
Sharad Verma, Xinrong Tian, Louis Lafrance, Céline Duquenne, Dominic Suarez, Kenneth Newlander, Stuart Romeril, Joelle Burgess, Seth Grant, James Brackley, Alan Graves, Daryl Scherzer, Art Shu, Christine Thompson, Heidi Ott, Glenn S Aller, Carl Machutta, Elsie Diaz, Yong Jiang, Neil Johnson, Steven Knight, Ryan Kruger, Michael Mccabe, Dashyant Dhanak, Peter Tummino, Caretha Creasy, William Miller