2. Academic Validation
  3. Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity

Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity

  • ACS Med Chem Lett. 2019 Mar 15;10(5):737-742. doi: 10.1021/acsmedchemlett.8b00631.
Toru Taniguchi 1,  Hiroaki Inagaki 1,  Daichi Baba 2,  Isao Yasumatsu 3,  Akiko Toyota 1,  Yasuyuki Kaneta 1,  Masaki Kiga 1,  Shin Iimura 1,  Takashi Odagiri 1,  Yoshihiro Shibata 1,  Kiyono Ueda 4,  Maki Seo 4,  Hiroki Shimizu 4,  Tomoki Imaoka 1,  Kiyoshi Nakayama 2
Affiliations

Affiliations

  • 1 R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 2 Daiichi Sankyo Co., Ltd., 3-5-1 Nihonbashi-honcho, Chuo-ku, Tokyo 103-8426, Japan.
  • 3 Daiichi Sankyo RD Novare Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 4 Daiichi Sankyo RD Novare Co., Ltd., 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
PMID: 31097992 DOI: 10.1021/acsmedchemlett.8b00631
Abstract

To obtain a new Anticancer drug, we focused on FER tyrosine kinase. Starting with high-throughput screening with our in-house chemical library, compound 1, which has a pyridine moiety, was found. Referring to their X-ray crystal structure with FES proto-oncogene tyrosine kinase, as a surrogate of FER followed by chemical modification including scaffold hopping of the pyridine template, we discovered pyrido-pyridazinone derivatives with potent FER kinase inhibitory activity. Here, we disclose the structure-activity relationship on the scaffold and representative compound 21 (DS21360717), which showed in vivo antitumor efficacy in a subcutaneous tumor model.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-128576
    99.93%, FER Tyrosine Kinase Inhibitor