2. Academic Validation
  3. Identification of ortho-hydroxy anilide as a novel scaffold for lysine demethylase 5 inhibitors

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

  • Bioorg Med Chem Lett. 2019 May 15;29(10):1173-1176. doi: 10.1016/j.bmcl.2019.03.028.
Pattaporn Jaikhan 1,  Benjaporn Buranrat 2,  Yukihiro Itoh 1,  Jiranan Chotitumnavee 1,  Takashi Kurohara 1,  Takayoshi Suzuki 3
Affiliations

Affiliations

  • 1 Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan.
  • 2 Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan; Biomedical Sciences Research Unit, Faculty of Medicine, Mahasarakham University, Muang District, Maha Sarakham 44000, Thailand.
  • 3 Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan; CREST, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: suzukit@koto.kpu-m.ac.jp.
PMID: 30928196 DOI: 10.1016/j.bmcl.2019.03.028
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

Drug design; Histone deacetylase; Inhibitor; Lysine demethylase; Small molecule.

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