CAMBRIDGE, Mass., Oct. 1, 2012 /PRNewswire/ -- Epizyme, Inc., a company leading the creation of a new class of personalized therapeutics for patients with genetically defined cancers, announced today the publication of breakthrough research in the treatment of genetically defined lymphomas, in the journal Nature Chemical Biology.
Epizyme’s landmark research demonstrates for the first time that a potent, small molecule inhibitor selectively kills lymphoma cells bearing genetic mutations in EZH2, a histone methyltransferase (HMT). HMTs are an important epigenetic target class, with genetic alterations strongly associated with the development of several types of cancer. Cancers with genetic alterations of EZH2 require EZH2 enzymatic activity for proliferation, suggesting that EZH2 is a driving oncogene in these cancers.
“This publication shows that Epizyme’s proprietary EZH2 inhibitor EPZ5687 selectively kills lymphoma cells bearing change-of-function mutations in EZH2 by permeating cells and selectively inhibiting H3K27 methylation, without an effect on any other histone methyl marks,” said Kevin Kuntz, Ph.D., Associate Director of Chemistry, Epizyme and a corresponding author of the paper. “This paper demonstrates Epizyme’s leadership in translating breakthroughs in biological understanding into personalized therapeutics for genetically defined cancers.”
Key findings from the paper include:
- Epizyme’s HMT inhibitor (HMTi), EPZ5687, selectively kills tumor cells bearing a genetic mutation in EZH2 with minimal effects on cells that do not bear the mutation.
- EPZ5687 is a potent inhibitor of EZH2 (Ki of 24 nM) with greater than 500-fold selectivity compared to other HMTs.
- EZH2 inhibition with EPZ5687 directly correlates with specific tumor cell killing through the selective reduction of methylation of the EZH2 substrate, histone H3 at lysine 27 (H3K27).
- EZH2 is a driving oncogene, as cancers with genetic change-of-function alterations of EZH2 (e.g., Tyr641 or Ala677 mutations) require EZH2 enzymatic activity for proliferation.
“These results provide compelling support for the hypothesis that the change-of-function mutations in EZH2 in a set of patients with non-Hodgkin’s lymphoma are oncogenic, playing a driving role in the development of cancer in these patients. The dependency of these cancers on altered EZH2 activity suggests the potential of EZH2 inhibitors as personalized cancer therapeutic agents,” said Eric Hedrick, M.D., Chief Medical Officer, Epizyme.
The paper titled, “A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells,” was authored by Sarah K. Knutson, Tim J. Wigle and colleagues at Epizyme, and is available online.
About Epizyme
Epizyme is leading the creation of small molecule histone methyltransferase inhibitors (HMTi), a new class of personalized therapeutics for patients with genetically defined cancers. Genetic alterations in HMTs, a family of epigenetic enzymes, drive multiple human diseases. Our approach represents the future of healthcare by matching better medicines with the right patients.
Epizyme has benchmark partnerships with Celgene, GSK and Eisai and receives funding and strategic support from the Multiple Myeloma Research Foundation (MMRF) and the Leukemia & Lymphoma Society (LLS). For more information, visit www.epizyme.com.
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