Research outline

 Taisho Pharmaceutical Co., Ltd. , Mitsubishi Tanabe Pharma Corporation, KYORIN Pharmaceutical Co.,Ltd, SHIMADZU CORPORATION and other 26 companies supported to open Sugiyama laboratory as a research funder

 

 

§  --Aim to establish an integrative drug development supporting system based on prediction of Pharmacokinetics, drug efficacy, and drug toxicity-

 Dr. Ryoji Noyori, President,IKEN invited Dr. Yuichi Sugiyama, Laboratory of Molecular Pharmacokinetics, University of Tokyo and opened a Sugiyama laboratory, RIKEN Innovation Center, RIKEN Cluster for Industry Partnerships on April 1, 2012.  Taisho Pharmaceutical Co., Ltd. , Mitsubishi Tanabe Pharma Corporation, KYORIN Pharmaceutical Co., Ltd, SHIMADZU CORPORATION and other 26 companies supported to open Sugiyama laboratory as research funder.

 Sugiyama laboratory utilizes special laboratory programwhich aim to invite distinguished researchers and encourage them to establish  an integrative drug development supporting system that will be able to predict disease state variation, interindividual variability, drug interaction, and about pharmacokinetics, drug efficacy, and drug toxicity from in vitro to in vivo.

 Concretely, the project will develop a prediction system for drug interactions by using modeling and simulation with considering the time course of both perpetrator and victim drugs. Our goal is to generate virtual humans data considering clinical and pathophysiological state, gender /age/ethnic difference and then build a prediction system to evaluate a special populations’s pharmacokinetic or interindividual variability of therapeutic and adverse effects  without real clinical studies. This prediction system will be also helpful to build a criteria whether we need to do microdose study and/or positron-emission tomography study or not.  By development of the system, it will have possibility to improve current situation that a lot of the pipeline compounds  are withdrawan during the clinical  development although  they already get into clinical investigation stage.  We can thus expect that efficient drug development system will be established.  

  RIKEN is only one multidiscipline research institute for nature science in Japan. We conduct a research which covers a wide range of science fields such as physics, engineering, chemistry, biology, medical science and so on. There are “RIKEN Center for Molecular Imaging Science” which is a core base of research for the molecular imaging science and “Omics science center” which promotes research support for life science research field.  Sugiyama laboratory will work with those centers and aim to establish an integrative drug development supporting system to accelerate new drug development in Japan.


 1.     background and effort

 

 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 transport (related to pharmacokinetics) will be studied by 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 clinical trials require a lot of money, 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.