PlatformTechnology Platforms Specialized in Drug Discovery
and Medical Technology Research and Development
Drug Discovery and Medical Technology Platforms to Support One-Stop, Speedy
Research and Development at RIKEN
Wide-ranging technology platforms are necessary for the research and development of new drugs and
medical technologies, and the technology platforms themselves should also be innovative in line
with the progress in life science research. In drug discovery research, we identify and validate
target proteins that cause diseases, create the seeds for drug discovery through a range of
screening approaches, optimize leads to identify drug candidates through medicinal chemistry,
and then proceed to preclinical studies. Consequently, in drug discovery research, the R&D
process is not completed by a single research laboratory but is advanced via an strategic
organizational orchestration that directs diverse technology platforms. RIKEN Drug Discovery and
Medical Technology Platforms have structured each drug discovery platform unit in each RIKEN
research centers.
We have three domains of research platforms for implementing drug discovery and medical
technology: 1) the basic research domain to identify and validate drug discovery targets, 2) the
discovery research domain for screening and optimizing seeds and leads to identify candidates,
and 3) the translational research (TR) domain to conduct pre-clinical studies that evaluate the
profiles of clinical candidates including safety for advancing drugs to the clinical studies
(see the diagram below). To cover these research and development domains, we currently have ten
drug discovery units, and we collaborate with external experts or outsource technology platforms
that do not exist within internal research infrastructure.
Click on the following image to enlarge
Platform Unit Clusters and Cutting-Edge Training Platforms for Drug Discovery
and Medical Technology
Building a Network of Practical Technology Platforms and Promoting R&D
To support the research and development domains in implementing drug discovery and medical
technology, we have established the cutting-edge research technology platform units listed
below. In addition to basic functions, such as supporting drug discovery research, each platform
unit is developing proprietary technologies and know-hows and building technology platform
networks that are unique to the drug discovery in RIKEN.
Drug Discovery Chemical Bank Unit
Screening of Natural Compounds
The forte of the Drug Discovery Chemical Bank Unit contains 134,000 natural compounds
in the NPDepo (Natural Product Depository) and its database, NPEdia.
In addition to independent collection and storage of microbial secondary metabolites,
we promote the depository of natural compound information by making the database of
compounds available to the public online. We support screening studies to analyze
the interaction between natural compounds and proteins.
Drug Discovery Computational Chemistry Platform Unit
High-precision In Silico Screening Using the Latest Modeling Theories and
Statistical Theories
At the Drug Discovery Computational Chemistry Platform Unit, we implement
high-precision in silico screening based on cutting-edge technologies in both
molecular simulations and artificial intelligence, using the three-dimensional
structure of target proteins and wet screening results of known inhibitors. Our
strong points are machine learning and quantum chemical calculations, and
facilitating drug design for improving ADMET profile.
Preparation, Interaction analysis, and Structural Analysis of Target Proteins
The Drug Discovery Structural Biology Platform Unit prepares protein samples for
various purposes and performs interaction analysis of drug candidates with their
target proteins using physicochemical methods along with structural analysis of
their complexes to optimize antibody drug candidates and small molecules.
Medicinal chemistry in small molecule drug discovery
The drug discovery chemistry platform unit performs “Hit to Lead” optimization of HTS
hits identified in the Drug discovery seed compound exploratory unit, where chemical
structures of the HTS hits are synthetically modified for improved in vitro
activity, selectivity and pharmacokinetics in order to verify desired in vivo
efficacy in animal disease models.
In the “Hit to Lead” stage, applications of the latest drug discovery technologies
such as in silico docking simulations by the Drug discovery computational chemistry
platform unit, and X-ray crystallographic analysis by the Drug discovery structural
biology platform unit proved particularly effective. Lead compounds identified in
this process are further optimized for in vivo efficacy and toxicity profiles (“Lead
optimization”) for preclinical candidate identification.
This unit develops, constructs, and applies in-silico drug design strategies
utilizing dynamical information on protein structure obtained using MDGRAPE-4A, a
special-purpose computer system for molecular dynamics simulations.
Discovering Seed Compounds by High-Throughput Screening to Develop New Drugs
The Drug Discovery Seed Compounds Exploratory Unit aims to identify seed compounds
for drug discovery by high-throughput Screening (HTS) using in vitro and cell-based
assay systems.
Generation of monoclonal antibodies as antibody drug with proprietary technology
for clinical application
Drug Discovery Antibody Platform Unit generates monoclonal antibodies against target
molecules for treatment of diseases by rapid screening technology and contribute to
clinical application.
This unit carries out the following using disease-specific iPS cells deposited at
the RIKEN BRC Cell Bank.
Searching for and identification of target cells (disease-causing and/or associated
cells), their phenotypic analyses, development of methods to efficiently and
abundantly induce those target cells, assay development for drug screening based on
phenotypes of cells, and production and supply of target cells for drug screening.
In collaboration with other units of DMP, this unit aims to contribute to innovative
drug discovery using disease-specific iPS cells.
Creating Cellular Drugs from a New Modality Developed at RIKEN
Artificial adjuvant vector cell (aAVC) has been created at RIKEN as a unique cellular
medicine platform. We are promoting drug discovery research using aAVC to develop
new therapeutic agents for the treatment of cancer and infectious diseases.
The objective of this unit is to conduct preclinical studies to prepare for clinical
trials on “target antigens,” that have been confirmed in basic immunological
studies.
Application of artificial intelligence technology to drug discovery and
development
Artificial intelligence (AI) has made rapid progress in recent years and is
contributing to various innovations. There are also great expectations for AI in
drug discovery.In addition, with the progress of digitalization, diverse and an
enormous amount of information is being generated and accumulated in the field of
drug discovery.
Utilizing such big data to bring about innovation is necessary. R-CCS AI-driven Drug
Discovery Collaborative Unit is conducting various research with the aim of
establishing innovative drug discovery strategies using AI and big data. In
addition, various simulations using high-performance computing represented by the
supercomputer "Fugaku" are rapidly developing, and we are also conducting research
that links simulations and AI.
