Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor

• Published in: Cancer science Vol. 108; no. 10; pp. 2069 - 2078
• Main Authors: Honma, Daisuke, Kanno, Osamu, Watanabe, Jun, Kinoshita, Junzo, Hirasawa, Makoto, Nosaka, Emi, Shiroishi, Machiko, Takizawa, Takeshi, Yasumatsu, Isao, Horiuchi, Takao, Nakao, Akira, Suzuki, Keisuke, Yamasaki, Tomonori, Nakajima, Katsuyoshi, Hayakawa, Miho, Yamazaki, Takanori, Yadav, Ajay Singh, Adachi, Nobuaki
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2017; John Wiley and Sons Inc
• Subjects: Administration, Oral; AML1 protein; Animals; Antitumor activity; Binding sites; Bioavailability; Biological Availability; Cancer; Cell differentiation; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Chromatin remodeling; Colorectal cancer; Drug Screening Assays, Antitumor - methods; Dual inhibitor; Employees; Enhancer of Zeste Homolog 2 Protein - antagonists & inhibitors; Enhancer of Zeste Homolog 2 Protein - chemistry; EZH1; EZH2; Gene expression; H3K27me3; Histone H3; histone methyltransferase; Homocysteine; Humans; Lethality; Lymphocytes B; Lymphoma; Lysine; Methyltransferase; Models, Molecular; Multiple myeloma; Mutation; NMR; Nuclear magnetic resonance; Original; Ovarian cancer; Polycomb group proteins; Polycomb-Group Proteins - antagonists & inhibitors; Polycomb-Group Proteins - chemistry; Rats; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacokinetics; Small Molecule Libraries - pharmacology; Stem cells; Structure-Activity Relationship; Sucrose; Therapeutic applications; Toxicity; Tumor cell lines; Tumorigenesis; Tumors; histone methyltransferase; Dual inhibitor; EZH1; EZH2; H3K27me3

Polycomb repressive complex 2 (PRC2) methylates histone H3 lysine 27 and represses gene expression to regulate cell proliferation and differentiation. Enhancer of zeste homolog 2 (EZH2) or its close homolog EZH1 functions as a catalytic subunit of PRC2, so there are two PRC2 complexes containing eit...