TY - JOUR
T1 - Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity
AU - Suzuki, Takayoshi
AU - Ozasa, Hiroki
AU - Itoh, Yukihiro
AU - Zhan, Peng
AU - Sawada, Hideyuki
AU - Mino, Koshiki
AU - Walport, Louise
AU - Ohkubo, Rei
AU - Kawamura, Akane
AU - Yonezawa, Masato
AU - Tsukada, Yuichi
AU - Tumber, Anthony
AU - Nakagawa, Hidehiko
AU - Hasegawa, Makoto
AU - Sasaki, Ryuzo
AU - Mizukami, Tamio
AU - Schofield, Christopher J.
AU - Miyata, Naoki
PY - 2013/9/26
Y1 - 2013/9/26
N2 - Histone Nε-methyl lysine demethylases KDM2/7 have been identified as potential targets for cancer therapies. On the basis of the crystal structure of KDM7B, we designed and prepared a series of hydroxamate analogues bearing an alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A, KDM7A, and KDM7B, with IC50s of 6.8, 0.2, and 1.2 μM, respectively. While inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7-subfamily inhibitor 9 exerted antiproliferative activity, indicating the potential for KDM2/7 inhibitors as anticancer agents.
AB - Histone Nε-methyl lysine demethylases KDM2/7 have been identified as potential targets for cancer therapies. On the basis of the crystal structure of KDM7B, we designed and prepared a series of hydroxamate analogues bearing an alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A, KDM7A, and KDM7B, with IC50s of 6.8, 0.2, and 1.2 μM, respectively. While inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7-subfamily inhibitor 9 exerted antiproliferative activity, indicating the potential for KDM2/7 inhibitors as anticancer agents.
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U2 - 10.1021/jm400624b
DO - 10.1021/jm400624b
M3 - Article
C2 - 23964788
AN - SCOPUS:84884997299
VL - 56
SP - 7222
EP - 7231
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 18
ER -
