1. Academic Validation
  2. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2

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

  • ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6. doi: 10.1021/ml3003346.
Sharad K Verma 1 Xinrong Tian 1 Louis V LaFrance 1 Céline Duquenne 1 Dominic P Suarez 1 Kenneth A Newlander 1 Stuart P Romeril 1 Joelle L Burgess 1 Seth W Grant 1 James A Brackley 1 Alan P Graves 1 Daryl A Scherzer 1 Art Shu 1 Christine Thompson 1 Heidi M Ott 1 Glenn S Van Aller 1 Carl A Machutta 1 Elsie Diaz 1 Yong Jiang 1 Neil W Johnson 1 Steven D Knight 1 Ryan G Kruger 1 Michael T McCabe 1 Dashyant Dhanak 1 Peter J Tummino 1 Caretha L Creasy 1 William H Miller 1
Affiliations

Affiliation

  • 1 Cancer Epigenetics Discovery Performance Unit, Oncology Research & Development, Protein Dynamics Discovery Performance Unit, Oncology Research & Development, and Platform Technology and Sciences, GlaxoSmithKline Pharmaceuticals , Collegeville, Pennsylvania 19426, United States.
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.

Keywords

EZH2; Epigenetics; H3K27me3; PRC2; SAM-competitive inhibitor; methyltransferase.

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