Centers & Labs

RIKEN Innovation Center

Sugiyama Laboratory

Head of Sugiyama Laboratory: Yuichi Sugiyama (Ph.D.)
Yuichi  Sugiyama(Ph.D.)

Many drug candidate compounds are synthesized in the early stage of a drug discovery. For these drug candidates, binding affinities to the target molecule (related to pharmacodynamics), rates of metabolism and membrane transports (related to pharmacokinetics) will be studied using in vitro experiments. By comparing the various parameters obtained in these experiments, drug candidates will be selected and introduced into clinical trials. However, efficacies expected from animal experiments and in vitro experiments are not always reproducible in clinical trials, and it is also true that most of drug candidates drop out before the market. Since it costs much in clinical trials, it is very important to select good drug candidates before going to the stage of clinical trials. RIKEN established Sugiyama Laboratory to promote the construction of an integrated support system for efficient drug discovery. In Sugiyama Laboratory, we will establish a new methodology to select a reasonable drug candidates in the early stages of drug discovery. In particular, mathematical models that incorporate parameters obtained from a variety of in vitro screening will be constructed, which can be used for the quantitative simulation of pharmacokinetics and pharmacodynamics. Thus, before entering the clinical trials, we will accurately predict the efficacy of each drug candidate in human. In addition, PET molecular imaging which enables the real-time and non-invasive quantification of PET-probed drugs and drug candidates in organs should be useful for the optimization of our mathematical models. In the future, our research will lead to the development of drugs that have wide therapeutic ranges or that can be less affected by drug-drug interactions, inter-individual variation and disease states.

Main Research Field

Medicine, dentistry, and pharmacy

Related Research Fields

Complex systems / Biological Sciences

Keywords

  • Transporter
  • Drug metabolism and pharmacokinetics
  • Pharmacokinetics/pharmacodynamics
  • Genetic polymorphism/ Personalized medicine
  • Drug interaction

Selected Publications

  1. Yamada A, Maeda K, Kiyotani K, Mushiroda T, Nakamura Y, Sugiyama Y.:
    "Kinetic Interpretation of the Importance of OATP1B3 and MRP2 in Docetaxel-Induced Hematopoietic Toxicity"
    CPT Pharmacometrics Syst Pharmacol 3: e126 (2014).
  2. Izumi S, Nozaki Y, Maeda K, Komori T, Takenaka O, Kusuhara H and Sugiyama Y.:
    "Investigation of the Impact of Substrate Selection on In Vitro Organic Anion Transporting Polypeptide 1B1 Inhibition Profiles for the Prediction of Drug-Drug Interactions"
    Drug Metab Dispos 43:235-247 (2015).
  3. Yamashita, M. Kataoka, Y. Suzaki, H. Imai, T. Morimoto, K. Ohashi, A. Inano, K. Togashi, K. Mutaguchi, and Y. Sugiyama:
    "An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development"
    J Pharm Sci 104 (9):3154-61 (2015).
  4. S. J. Kim, T. Yoshikado, I. Ieiri, K. Maeda, M. Kimura, S. Irie, H. Kusuhara, and Y. Sugiyama.
    "Clarification of the Mechanism of Clopidogrel-Mediated Drug-Drug Interaction in a Clinical Cassette Small-Dose Study and Its Prediction Based on in Vitro Information"
    Drug Metab Dispos 44: 1622-32 (2016).
  5. A. Ose, K. Toshimoto, K. Ikeda, K. Maeda, S. Yoshida, F. Yamashita, M. Hashida, T. Ishida, Y. Akiyama, and Y. Sugiyama:
    "Development of a Support Vector Machine-Based System to Predict Whether a Compound Is a Substrate of a Given Drug Transporter Using Its Chemical Structure"
    J Pharm Sci 105: 2222-30 (2016).
  6. J. Takano, K. Maeda, M. B. Bolger, and Y. Sugiyama:
    "The Prediction of the Relative Importance of Cyp3a/P-Glycoprotein to the Nonlinear Intestinal Absorption of Drugs by Advanced Compartmental Absorption and Transit Model"
    Drug Metab Dispos 44:1808-18:(2016).
  7. Yoshikado T, Yoshida K, Kotani N, Nakada T, Asaumi R, Toshimoto K, Maeda K, Kusuhara H, Sugiyama Y.:
    "Quantitative Analyses of Hepatic OATP-Mediated Interactions Between Statins and Inhibitors Using PBPK Modeling With a Parameter Optimization Method"
    Clin Pharmacol Ther 100 (5):513-523 (2016).
  8. M. Ito, H. Kusuhara, A. Ose, T. Kondo, K. Tanabe, H. Nakayama, S. Horita, T. Fujita, Y. Sugiyama.:
    "Pharmacokinetic Modeling and Monte Carlo Simulation to Predict Interindividual Variability in Human Exposure to Oseltamivir and Its Active Metabolite, Ro 64-0802"
    AAPS J 19 (1):286-297 (2017).
  9. S. Izumi, Y. Nozaki, T. Komori, O. Takenaka, K. Maeda, H. Kusuhara, Y. Sugiyama.:
    "Comparison of the Predictability of Human Hepatic Clearance for Organic Anion Transporting Polypeptide Substrate Drugs Between Different In Vitro-In Vivo Extrapolation Approaches"
    J Pharm Sci 24 pii: (17):30084-9 (2017).
  10. Yoshikado T, Toshimoto K, Nakada T, Ikejiri K, Kusuhara H, Maeda K, Sugiyama Y.:
    "Comparison of Methods for Estimating Unbound Intracellular-to-Medium Concentration Ratios in Rat and Human Hepatocytes Using Statins"
    Drug Metab Dispos. 45(7):779-789 (2017).

Lab Members

Principal Investigator

Yuichi Sugiyama
Head of Sugiyama Laboratory

Core Members

Takashi Yoshikado
Research Scientist
Aya Kiriake
Research Scientist
Kota Toshimoto
Postdoctoral Researcher
Kyeong Ryoon Lee
Visiting Scientist
Sae Hee Kim
Visiting Scientist
Insoo Yoon
Visiting Scientist
Atsuko Tomaru
Visiting Scientist
Kiyoe Morita
Technical Staff I
Keiko Ishigame
Technical Staff II
Hisako Motokawa
Technical Staff II
Sachie Satoh
Assistant
Chinami Yamada
Assistant
Aya Miyamoto
Part-time Worker
Rie Abe
Part-time Worker
Yukio Kato
Senior Visiting Scientist
Akihiro Hisaka
Senior Visiting Scientist
Kazuya Maeda
Senior Visiting Scientist
Kiyomi Ito
Visiting Scientist
Ichiro Ieiri
Visiting Scientist
Fumiyoshi Yamashita
Visiting Scientist
Maki Yoneko
Visiting Scientist
Hiroyuki Kusuhara
Visiting Scientist
Seiji Miyauchi
Visiting Scientist
Koji Chiba
Visiting Scientist
Katsuhisa Inoue
Visiting Scientist
Kousei Ito
Visiting Scientist

Contact information

1-7-22 Suehiro-cho, Tsurumi-ku
Yokohama, Kanagawa
230-0045, Japan
Tel: +81-(0)45-503-9210
Fax: +81-(0)45-506-9190

Email: ychi.sugiyama [at] riken.jp

Related links