2. Academic Validation
  3. 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.
PMID: 24900432 DOI: 10.1021/ml3003346
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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