1. Academic Validation
  2. EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

  • ACS Med Chem Lett. 2015 Mar 4;6(5):491-5. doi: 10.1021/acsmedchemlett.5b00037.
John E Campbell 1 Kevin W Kuntz 1 Sarah K Knutson 1 Natalie M Warholic 1 Heike Keilhack 1 Tim J Wigle 1 Alejandra Raimondi 1 Christine R Klaus 1 Nathalie Rioux 1 Akira Yokoi 2 Satoshi Kawano 2 Yukinori Minoshima 2 Hyeong-Wook Choi 3 Margaret Porter Scott 1 Nigel J Waters 1 Jesse J Smith 1 Richard Chesworth 1 Mikel P Moyer 1 Robert A Copeland 1


  • 1 Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States.
  • 2 Eisai Co., Ltd. , Tokodai 5-1-3, Tsukuba, Ibarakai 300-2635, Japan.
  • 3 Eisai, Inc. , 4 Corporate Drive, Andover, Massachusetts 01810, United States.

Inhibitors of the protein methyltransferase Enhancer of Zeste Homolog 2 (EZH2) may have significant therapeutic potential for the treatment of B cell lymphomas and other Cancer indications. The ability of the scientific community to explore fully the spectrum of EZH2-associated pathobiology has been hampered by the lack of in vivo-active tool compounds for this enzyme. Here we report the discovery and characterization of EPZ011989, a potent, selective, orally bioavailable inhibitor of EZH2 with useful pharmacokinetic properties. EPZ011989 demonstrates significant tumor growth inhibition in a mouse xenograft model of human B cell lymphoma. Hence, this compound represents a powerful tool for the expanded exploration of EZH2 activity in biology.


B cell lymphoma; EZH2; KARPAS-422; Methyltransferase; PRC2; in vivo chemical probe; xenograft.