Development of novel bisubstrate-type inhibitors of histone methyltransferase SET7/9

被引：47

作者：

Mori, Shuichi ^{[2
]}

Iwase, Kenta ^{[2
]}

Iwanami, Naoko ^{[1
]}

Tanaka, Yujiro ^{[2
]}

Kagechika, Hiroyuki ^{[1
,2
]}

Hirano, Tomoya ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, Tokyo 1010062, Japan

[2] Tokyo Med & Dent Univ, Grad Sch Biomed Sci, Chiyoda Ku, Tokyo 1010062, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 23期

关键词：

Histone methyltransferase; Small molecule inhibitor; Bisubstrate inhibitor; Epigenetics; SET7/9; RATIONAL DESIGN; P53; ACTIVITY; ANALOG; AMINES;

D O I：

10.1016/j.bmc.2010.10.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Histone modification, for example, by histone deacetylase (HDAC) and histone lysine methyltransferase (HMT), plays an important role in regulating gene expression. To obtain novel inhibitors as tools for investigating the physiological function of members of the HMT family, we designed and synthesized novel inhibitors, which are amine analogues of adenosylmethionine (AdoMet; the cofactor utilized in the methylation reaction) bearing various alkylamino groups coupled via an ethylene linker. The inhibitory activities of these compounds towards SET7/9, an HMT, were evaluated. It was found that introduction of an alkylamino group increased the inhibitory activity. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：8158 / 8166

页数：9

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