2. Academic Validation
  3. Discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by the use of docking models

Discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by the use of docking models

  • Bioorg Med Chem Lett. 2019 Jan 1;29(1):115-118. doi: 10.1016/j.bmcl.2018.10.051.
Kazutaka Ikegashira 1,  Taku Ikenogami 1,  Takayuki Yamasaki 1,  Yasunori Hase 1,  Takayuki Yamaguchi 1,  Koji Inagaki 1,  Satoki Doi 1,  Tsuyoshi Adachi 1,  Yoshihisa Koga 1,  Hiromasa Hashimoto 1
Affiliations

Affiliation

  • 1 Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
PMID: 30442420 DOI: 10.1016/j.bmcl.2018.10.051
Abstract

We report the discovery of a novel azetidine scaffold for colony stimulating factor-1 receptor (CSF-1R) Type II inhibitors by using a structure-based drug design (SBDD) based on a docking model. The work leads to the representative compound 4a with high CSF-1R inhibitory activity (IC50 = 9.1 nM). The obtained crystal structure of an azetidine compound with CSF-1R, which matched our predicted docking model, demonstrates that the azetidine compounds bind to the DFG-out conformation of the protein as a Type II inhibitor.

Keywords

Azetidine scaffold; CSF-1R; DFG-out; Type II inhibitor; cFMS.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-119942
    99.47%, CSF-1R Type 2 Inhibitor