2. Academic Validation
  3. Discovery of DS79182026: A potent orally active hepcidin production inhibitor

Discovery of DS79182026: A potent orally active hepcidin production inhibitor

  • Bioorg Med Chem Lett. 2017 Aug 15;27(16):3716-3722. doi: 10.1016/j.bmcl.2017.07.004.
Takeshi Fukuda 1,  Riki Goto 2,  Toshihiro Kiho 3,  Kenjiro Ueda 4,  Sumie Muramatsu 4,  Masami Hashimoto 4,  Anri Aki 2,  Kengo Watanabe 5,  Naoki Tanaka 6
Affiliations

Affiliations

  • 1 Rare Disease & LCM Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: [email protected].
  • 2 Biologics & Immuno-Oncology Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 3 Modality Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 4 Pain & Neuroscience Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 5 Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 6 Rare Disease & LCM Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
PMID: 28705644 DOI: 10.1016/j.bmcl.2017.07.004
Abstract

Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. Inhibition of hepcidin could be a strategy favorable to treating anemia of chronic disease (ACD). We report herein the synthesis and structure-activity relationships (SARs) of a series of benzisoxazole compounds as orally active hepcidin production inhibitors. The optimization study of multi kinase inhibitor 1 led to a potent and bioavailable hepcidin production inhibitor 38 (DS79182026), which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model.

Keywords

Anemia of chronic disease; Benzisoxazole; Hepcidin; Kinase; Pyrazole.

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