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

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.

SUBMITTER: Lu B

PROVIDER: S-EPMC5807876 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Lu Biao B Shen Xiaodong X Zhang Lei L Liu Dong D Zhang Caihua C Cao Jingsong J Shen Ru R Zhang Jiayin J Wang Dan D Wan Hong H Xu Zhibin Z Ho Ming-Hsun MH Zhang Minsheng M Zhang Lianshan L He Feng F Tao Weikang W

ACS medicinal chemistry letters 20180129 2

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 developm ...[more]

PMID: 29456795

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