Discovery of EBI-2511: A Highly Potent and Orally Active EZH2 Inhibitor for the Treatment of Non-Hodgkin's Lymphoma

  • ACS Med Chem Lett. 2018 Jan 29;9(2):98-102. doi: 10.1021/acsmedchemlett.7b00437.
Biao Lu  1 ,  Xiaodong Shen  1 ,  Lei Zhang  1 ,  Dong Liu  2 ,  Caihua Zhang  1 ,  Jingsong Cao  2 ,  Ru Shen  2 ,  Jiayin Zhang  2 ,  Dan Wang  1 ,  Hong Wan  1 ,  Zhibin Xu  1 ,  Ming-Hsun Ho  1 ,  Minsheng Zhang  2 ,  Lianshan Zhang  1 ,  Feng He  1 ,  Weikang Tao  1
Affiliations
  • 1. Shanghai Hengrui Pharmaceutical Co. Ltd., 279 Wenjing Road, Minhang Hi-tech Zone, Shanghai 200245, China.
  • 2. Eternity Bioscience Inc., 6 Cedarbrook Drive, Cranbury, New Jersey 08512, United States.
PMID: 29456795 DOI: 10.1021/acsmedchemlett.7b00437
Abstract

A novel series of benzofuran derived EZH2 inhibitors were discovered through a scaffold hopping approach based on the clinical compound of EPZ-6438. Further rational structure-activity relationship exploration and optimization led to the discovery of more potent EZH2 inhibitors with oral bioavailability in mice and rats. A lead compound EBI-2511 (compound 34) demonstrated excellent in vivo efficacy in Pfeiffer tumor Xenograft models in mouse and is under preclinical development for the treatment of cancers associated with EZH2 mutations.

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