Toward the development of potent and selective bisubstrate inhibitors of protein arginine methyltransferases

被引：65

作者：

Dowden, James ^{[1
]}

Hong, Wei ^{[1
]}

Parry, Richard V. ^{[2
]}

Pike, Richard A. ^{[1
]}

Ward, Stephen G. ^{[2
]}

机构：

[1] Univ Nottingham, Sch Chem, Nottingham NG7 2RD, England

[2] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 07期

基金：

英国医学研究理事会;

关键词：

Protein arginine methyltransferases; Small-molecule inhibitors; S-Adenosylmethionine; Methylation; Epigenetics; STABLE NITROGEN ANALOGS; METHYLATION; BINDING; ADOMET; DESIGN;

D O I：

10.1016/j.bmcl.2010.02.069

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Prototype inhibitors of protein arginine methyltransferases (PRMTs) have been constructed by attaching guanidine functionality via a variable linker to non-reactive amine analogues of the cellular co-factor (S)-adenosyl methionine (AdoMet). Potent inhibition of PRMT1 (IC50 of similar to 3-6 mu M) combined with weak inhibition of the lysine methyltransferase SET7 (similar to 50% of activity at 100 mu M) was observed for two such compounds. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2103 / 2105

页数：3

共 30 条

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Arginine methylation at a glance [J].