Drug Discovery Structural Biology Platform Unit | RIKEN BDR

Drug Discovery Structural Biology Platform Unit

Unit Leader

Mikako ShirouzuPh.D.

Photo of principal investigator

  • 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

  • Kukimoto-Niino M, Katsura K, Kaushik R, et al.
    Cryo-EM structure of the human ELMO1-DOCK5 complex.
    Science Advances 7(30). eabg3147 (2021) doi: 10.1126/sciadv.abg3147
  • Mizuta H, Okada K, Araki M, et al.
    Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer.
    Nature Communications 12(1). 1261 (2021) doi: 10.1038/s41467-021-21396-w.
  • Yamamoto H, Sakai N, Ohte S, et al.
    Novel bicyclic pyrazoles as potent ALK2 (R206H) inhibitors for the treatment of fibrodysplasia ossificans progressiva.
    Bioorganic & medicinal chemistry letters 38127858 (2021) doi: 10.1016/j.bmcl.2021.127858.
  • Nara T, Nakagawa Y, Tsuganezawa K, et al.
    The ubiquinone synthesis pathway is a promising drug target for Chagas disease.
    PLoS ONE 16(2). e0243855 (2021) doi: 10.1371/journal.pone.0243855.
  • Kobayashi H, Hatakeyama H, Nishimura H, et al.
    Chemical reversal of abnormalities in cells carrying mitochondrial DNA mutations.
    Nature Chemical Biology 17(3). 335-343 (2021) doi: 10.1038/s41589-020-00676-4.
  • Takahashi K, Akatsu Y, Podyma-Inoue KA, et al.
    Targeting all transforming growth factor-beta isoforms with a Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer.
    Journal of Biological Chemistry 295(36), 12559-12572 (2020) doi: 10.1074/jbc.RA120.012492.
  • Sato T, Sekimata K, Sakai N, et al.
    Structural Basis of Activin Receptor-Like Kinase 2 (R206H) Inhibition by Bis-heteroaryl Pyrazole-Based Inhibitors for the Treatment of Fibrodysplasia Ossificans Progressiva Identified by the Integration of Ligand-Based and Structure-Based Drug Design Approaches.
    American Chemical Society 5(20). 11411-11423 (2020) doi: 10.1021/acsomega.9b04245.
  • Yasukawa M, Ando Y, Yamashita T, et al.
    CDK1 dependent phosphorylation of hTERT contributes to cancer progression.
    Nature Communications 11(1). 1557 (2020) doi: 10.1038/s41467-020-15289-7.
  • Tsuganezawa K, Sekimata K, Nakagawa Y, et al.
    Identification of small molecule inhibitors of human COQ7.
    Bioorganic & Medicinal Chemistry 28(1). 115182 (2020) doi: 10.1016/j.bmc.2019.115182.
  • Sekimata K, Sato T, Sakai N, et al.
    Bis-Heteroaryl Pyrazoles: Identification of Orally Bioavailable Inhibitors of Activin Receptor-Like Kinase-2 (R206H).
    Chemical and Pharmaceutical Bulletin 67(3). 224-235 (2019) doi: 10.1248/cpb.c18-00598.
  • Tanaka M, Ishige A, Yaguchi M, et al.
    Development of a simple new flow cytometric antibody-dependent cellular cytotoxicity (ADCC) assay with excellent sensitivity.
    Journal of Immunological Methods 464. 74-86 (2019) doi: 10.1016/j.jim.2018.10.014.