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Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors |
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| Authors: | Pattaporn Jaikhan Benjaporn Buranrat Yukihiro Itoh Jiranan Chotitumnavee Takashi Kurohara Takayoshi Suzuki |
| Affiliation: | 1. Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan;2. Biomedical Sciences Research Unit, Faculty of Medicine, Mahasarakham University, Muang District, Maha Sarakham 44000, Thailand;3. CREST, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan |
| Abstract: | Fe(II)/α-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. |
| Keywords: | Small molecule Drug design Histone deacetylase Lysine demethylase Inhibitor |
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