Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors

被引:6
|
作者
Jaikhan, Pattaporn [1 ]
Buranrat, Benjaporn [1 ,2 ]
Itoh, Yukihiro [1 ]
Chotitumnavee, Jiranan [1 ]
Kurohara, Takashi [1 ]
Suzuki, Takayoshi [1 ,3 ]
机构
[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Sakyo Ku, 1-5 Shimogamohangi Cho, Kyoto 6060823, Japan
[2] Mahasarakham Univ, Fac Med, Biomed Sci Res Unit, Muang Dist 44000, Maha Sarakham, Thailand
[3] Japan Sci & Technol Agcy JST, CREST, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan
关键词
Small molecule; Drug design; Histone deacetylase; Lysine demethylase; Inhibitor; HISTONE DEMETHYLASES; CANCER; DOMAIN; METHYLATION; MECHANISMS;
D O I
10.1016/j.bmcl.2019.03.028
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Fe(II)/alpha-ketoglutarate-dependent lysine demethylases (KDMs) are attractive drug targets for several diseases including cancer. In this study, we designed and screened ortho-substituted anilides that are expected to function as Fe(II) chelators, and identified ortho-hydroxy anilide as a novel scaffold for KDM5A inhibitors. Treatment of human lung cancer A549 cells with a prodrug form of 4-carboxy-2-hydroxy-formanilide (9c) increased trimethylated lysine 4 on histone H3 level, suggesting KDM5 inhibition in the cells.
引用
收藏
页码:1173 / 1176
页数:4
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