Authors
Masoud Vedadi, Dalia Barsyte-Lovejoy, Feng Liu, Sylvie Rival-Gervier, Abdellah Allali-Hassani, Viviane Labrie, Tim J Wigle, Peter A DiMaggio, Gregory A Wasney, Alena Siarheyeva, Aiping Dong, Wolfram Tempel, Sun-Chong Wang, Xin Chen, Irene Chau, Thomas J Mangano, Xi-ping Huang, Catherine D Simpson, Samantha G Pattenden, Jacqueline L Norris, Dmitri B Kireev, Ashutosh Tripathy, Aled Edwards, Bryan L Roth, William P Janzen, Benjamin A Garcia, Arturas Petronis, James Ellis, Peter J Brown, Stephen V Frye, Cheryl H Arrowsmith, Jian Jin
Publication date
2011/8
Journal
Nature chemical biology
Volume
7
Issue
8
Pages
566-574
Publisher
Nature Publishing Group US
Description
Protein lysine methyltransferases G9a and GLP modulate the transcriptional repression of a variety of genes via dimethylation of Lys9 on histone H3 (H3K9me2) as well as dimethylation of non-histone targets. Here we report the discovery of UNC0638, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets. UNC0638 treatment of a variety of cell lines resulted in lower global H3K9me2 levels, equivalent to levels observed for small hairpin RNA knockdown of G9a and GLP with the functional potency of UNC0638 being well separated from its toxicity. UNC0638 markedly reduced the clonogenicity of MCF7 cells, reduced the abundance of H3K9me2 marks at promoters of known G9a-regulated endogenous genes and disproportionately affected several genomic loci encoding microRNAs. In mouse embryonic stem cells, UNC0638 reactivated G9a …
Total citations
Scholar articles
M Vedadi, D Barsyte-Lovejoy, F Liu, S Rival-Gervier… - Nature chemical biology, 2011