Lysine-Specific Demethylase 1-Selective Inactivators: Protein-Targeted Drug Delivery Mechanism

被引：76

作者：

Ogasawara, Daisuke ^{[1
,2
]}

Itoh, Yukihiro ^{[1
]}

Tsumoto, Hiroki ^{[3
]}

Kakizawa, Taeko ^{[4
]}

Mino, Koshiki ^{[5
]}

Fukuhara, Kiyoshi ^{[4
]}

Nakagawa, Hidehiko ^{[2
]}

Hasegawa, Makoto ^{[5
]}

Sasaki, Ryuzo ^{[6
]}

Mizukami, Tamio ^{[5
]}

Miyata, Naoki ^{[2
]}

Suzuki, Takayoshi ^{[1
,7
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Kita Ku, Kyoto 6038334, Japan

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

[3] Kyoto Univ, World Leading Drug Discovery Res Ctr, Kyoto 6068501, Japan

[4] Organ Chem Natl Inst Hlth Sci, Tokyo 1588501, Japan

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

[6] Frontier Pharma Inc, Nagahama City, Shiga 5260829, Japan

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

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2013年 / 52卷 / 33期

基金：

日本学术振兴会;

关键词：

biological activity; drug delivery; drug design; kinetics; proteins; HISTONE DEMETHYLASE; STRUCTURAL BASIS; LSD1; INHIBITION; TRANS-2-PHENYLCYCLOPROPYLAMINE; ANALOGS;

D O I：

10.1002/anie.201303999

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

Drug drop off: Given that lysine-specific demethylase 1 (LSD1) could be potently and selectively inactivated by delivering phenylcyclopropylamine (PCPA), a weak and nonselective LSD1 inhibitor, directly to the enzyme's active site, a novel series of LSD1 inactivators (1) were designed. Biological and mechanistic studies indicate that 1 inhibits LSD1 potently and selectively. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

收藏

页码：8620 / 8624

页数：5

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