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

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

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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