EPZ011989，一种强效的、口服可用的EZH2抑制剂，具有强大的体内活性。
EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity.
作者信息
Campbell John E, Kuntz Kevin W, Knutson Sarah K, Warholic Natalie M, Keilhack Heike, Wigle Tim J, Raimondi Alejandra, Klaus Christine R, Rioux Nathalie, Yokoi Akira, Kawano Satoshi, Minoshima Yukinori, Choi Hyeong-Wook, Porter Scott Margaret, Waters Nigel J, Smith Jesse J, Chesworth Richard, Moyer Mikel P, Copeland Robert A
机构信息
Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02139, United States.
Eisai Co., Ltd. , Tokodai 5-1-3, Tsukuba, Ibarakai 300-2635, Japan.
出版信息
ACS Med Chem Lett. 2015 Mar 4;6(5):491-5. doi: 10.1021/acsmedchemlett.5b00037. eCollection 2015 May 14.
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.
蛋白质甲基转移酶zeste同源物2（EZH2）抑制剂在治疗B细胞淋巴瘤和其他癌症适应症方面可能具有显著的治疗潜力。由于缺乏针对该酶的体内活性工具化合物，科学界充分探索EZH2相关病理生物学谱的能力受到了阻碍。在此，我们报告了EPZ011989的发现和特性，它是一种强效、选择性、口服生物可利用的EZH2抑制剂，具有良好的药代动力学性质。EPZ011989在人B细胞淋巴瘤小鼠异种移植模型中显示出显著的肿瘤生长抑制作用。因此，该化合物是在生物学中进一步探索EZH2活性的有力工具。
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