Synthesis and biological activity of optically active NCL-1, a lysine-specific demethylase 1 selective inhibitor

被引：42

作者：

Ogasawara, Daisuke ^{[1
]}

Suzuki, Takayoshi ^{[1
,2
]}

Mino, Koshiki ^{[3
]}

Ueda, Rie ^{[1
]}

Khan, Mohammed Naseer Ahmed ^{[1
]}

Matsubara, Takuya ^{[1
]}

Koseki, Koichi ^{[3
]}

Hasegawa, Makoto ^{[3
]}

Sasaki, Ryuzo ^{[4
]}

Nakagawa, Hidehiko ^{[1
]}

Mizukami, Tamio ^{[3
]}

Miyata, Naoki ^{[1
]}

机构：

[1] Nagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Aichi 4678603, Japan

[2] Japan Sci & Technol Agcy JST, PRESTO, Kawaguchi, Saitama 3320012, Japan

[3] Nagahama Inst Biosci & Technol, Grad Sch Biosci, Shiga 5260829, Japan

[4] Frontier Pharma Inc, Shiga 5260829, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 12期

关键词：

Histone demethylase; Inhibitor; Epigenetic gene expression; Lysine-specific demethylase; MECHANISM-BASED INACTIVATOR; HISTONE DEMETHYLASE; STRUCTURAL BASIS; SILENCED GENES; LSD1; METHYLATION; TRANS-2-PHENYLCYCLOPROPYLAMINE; ANALOGS; REEXPRESSION;

D O I：

10.1016/j.bmc.2010.12.024

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：

Optically active (1S,2R)-NCL-1 and (1R,2S)-NCL-1 were synthesized and evaluated for their lysine-specific demethylase 1 inhibitory activity and cell growth inhibitory activity. In enzyme assays, the (1S,2R)-isomer was approximately four times more potent than the (1R, 2S)-isomer. In cell growth inhibition assays, the two isomers showed similar activity in HEK293 cells and SH-SY5Y cells, whereas the (1S, 2R)-isomer showed approximately four times more potent activity than the (1R, 2S)-isomer in HeLa cells. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3702 / 3708

页数：7

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