Drug Discovery Structural Biology Platform Unit | RIKEN BDR

Drug Discovery Structural Biology Platform Unit

Unit Leader

Mikako ShirouzuPh.D.

  • Location:Yokohama
  • E-mail:mikako.shirouzu[at]riken.jpPlease replace [at] with @.

Evaluation of candidate compounds and analysis of their complex structures for DMP activities.

Research Summary

RIKEN Program for Drug Discovery and Medical Technology (DMP) is developing new candidate drugs and technologies for drug discovery and medical treatment. As part of the activities, our unit carries out protein sample preparation, evaluation of candidate compounds in vitro and in a cell-based manner, and structural analysis of their complexes to improve monoclonal antibody drugs, vaccines, and candidate small molecular drugs. Our activities as experts of protein science and cell biology are indispensable for the rational drug development promoted by DMP.

Rational drug development based on structural analysis

Research Theme

  • Preparation of antigen proteins for monoclonal antibody drugs and vaccines
  • Preparation of target proteins for candidate compound evaluation and structural analysis
  • In vitro compound evaluations for small molecular drugs
  • Cell-based compound evaluations for small molecular drugs
  • Complex structural analysis for rational drug development

Main Publications List

  • Koda Y, Kikuzato K, Mikuni J, et al.
    Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors.
    Bioorganic & Medicinal Chemistry Letters 27(22). 4944-4998 (2017) doi:10.1016/j.bmcl.2017.10.012
  • Shoji S, Hanada K, Ohsawa N, Shirouzu M.
    Central catalytic domain of BRAP (RNF52) recognizes the types of ubiquitin chains and utilizes oligo-ubiquitin for ubiquitylation.
    Biochemical Journal 474(18). 3207-3226 (2017) doi:10.1042/BCJ20161104
  • Yuki H, Kikuzato K, Mikuni J, et al.
    Activity cliff for 7-substituted pyrrolo-pyrimidine inhibitors of HCK explained in terms of predicted basicity of the amine nitrogen.
    Bioorganic & Medicinal Chemistry 25(16). 4259-4264 (2017) doi:10.1016/j.bmc.2017.05.053
  • Amano Y, Kikuchi M, Sato S, et al.
    Development and crystallographic evaluation of histone H3 peptide with N-terminal serine substitution as a potent inhibitor of lysine-specific demethylase 1.
    Bioorganic & Medicinal Chemistry 25(9). 2617-2624 (2017) doi:10.1016/j.bmc.2017.03.016.
  • Tanaka A, Saito Y and Ishikawa F
    Drug discovery targeting AML stem cells
    Jikken Igaku 32(2). 179-183 (2014)
  • Takemoto Y, Ito A, Niwa H, et al.
    Identification of Cyproheptadine as an Inhibitor of SET Domain Containing Lysine Methyltransferase 7/9 (Set7/9) That Regulates Estrogen-Dependent Transcription.
    Journal of Medicinal Chemistry59(8). 3650-3660 (2016) doi:10.1021/acs.jmedchem.5b01732