Identification of cell-active lysine specific demethylase 1-selective inhibitors.
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.
Ueda
Rie
R
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Suzuki
Takayoshi
T
Mino
Koshiki
K
Tsumoto
Hiroki
H
Nakagawa
Hidehiko
H
Hasegawa
Makoto
M
Sasaki
Ryuzo
R
Mizukami
Tamio
T
Miyata
Naoki
N
D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006657:Histones / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D006657:Histones; D056466:Histone Demethylases; C495195:KDM1A protein, human