Identification of cell-active lysine specific demethylase 1-selective inhibitors

Rie Ueda; Takayoshi Suzuki; Koshiki Mino; Hiroki Tsumoto; Hidehiko Nakagawa; Makoto Hasegawa; Ryuzo Sasaki; Tamio Mizukami; Naoki Miyata

doi:10.1021/ja907055q

Identification of cell-active lysine specific demethylase 1-selective inhibitors

J Am Chem Soc. 2009 Dec 9;131(48):17536-7. doi: 10.1021/ja907055q.

Authors

Rie Ueda¹, Takayoshi Suzuki, Koshiki Mino, Hiroki Tsumoto, Hidehiko Nakagawa, Makoto Hasegawa, Ryuzo Sasaki, Tamio Mizukami, Naoki Miyata

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.

PMID: 19950987
DOI: 10.1021/ja907055q

Abstract

Lysine specific demethylase 1 (LSD1) plays a key role in the regulation of gene expression by removing the methyl groups from methylated Lys4 of histone H3 (H3K4). Here we report the identification of the first small-molecule LSD1-selective inhibitors. These inhibitors show in vivo H3K4-methylating activity and antiproliferative activity and should be useful as lead structures for anticancer drugs and as tools for studying the biological roles of LSD1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Catalytic Domain
Cell Line, Tumor
Cell Proliferation / drug effects
Crystallography, X-Ray
Drug Design
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / metabolism
Enzyme Inhibitors / pharmacology*
Histone Demethylases / antagonists & inhibitors*
Histone Demethylases / chemistry
Histones / metabolism
Humans
Models, Molecular
Substrate Specificity

Substances

Enzyme Inhibitors
Histones
Histone Demethylases
KDM1A protein, human