Novel screening method for identifying inhibitors of EZH2 methyltransferase

Tumor repressor genes, which inhibit tumor formation, can be "turned off" due to undesirable molecular changes affecting the chromosomes on which the genes reside. Understanding and being able to control these alterations could lead to new approaches for activating or inactivating genes linked to cancer. A novel, high-throughput screening method used to identify agents that can block one chemical modifier that plays a key role in some forms of cancer is described in ASSAY and Drug Development Technologies, a peer-reviewed journal published from Mary Ann Liebert, Inc., publishers (http://www.liebertpub.com). The article is available on the ASSAY and Drug Development Technologies website (http://www.liebertpub.com/adt).

Jeffrey Simard, Matthew Plant, Renee Emkey, and Violeta Yu, Amgen, Inc. (Cambridge, MA) present an optimized, robust assay for screening large numbers of chemical compounds against EZH2 methyltransferase. This enzyme is part of a multi-protein complex which can alter the methylation state of chromosomal proteins. Increased EZH2 methyltransferase activity has been associated with reduced expression of tumor repressor genes.

In the article "Development and Implementation of a High-Throughput AlphaLISA Assay for Identifying Inhibitors of EZH2 Methyltransferase" (http://online.liebertpub.com/doi/full/10.1089/adt.2012.481) the authors describe the use of AlphaLisa technology to detect methylation by EZH2 and emphasize that this approach should accelerate the identification of small molecule inhibitors for use as research tools and for development as novel anti-cancer therapeutics.