Drug Discovery Research Unit

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Drug Discovery Platform that Maximize the Drug Discovery Process

The drug discovery platform of the Drug Discovery Research Unit responds not only to small molecule compounds but also to various modalities of drug discovery. The huge amounts of high-quality and highly replicable data generated will be used to build new drug discovery processes such as AI drug discovery.

Four Process that are the Basis of Drug Discovery Research

In drug discovery research, there are four important processes; "Discover", "Create", "Evaluate", and "Control". The Drug Discovery Research Unit has sophisticated drug discovery platforms that support these processes.

"Discover" potential compounds for new drugs

Discover true lead compounds that are drug candidates by any means. High-throughput Screening (HTS), which uses proprietary technologies and a variety of detecting technologies, Scaffold platform, which uses Cheminformatics and parallel synthesis technologies to discover promising skeletal, Structure-Based Drug Design (SBDD), which designs compounds by three-dimensional structural analysis/computational chemistry of disease-target molecules and compounds, and natural product discovery, which uses proprietary microorganisms, are used to contribute to "Discover" processes through a variety of approaches.

Drug Discovery Research Platforms

Structure-Based Drug Designkeyboard_arrow_down
  • Structural analysis of proteins
  • Biophysics
  • Virtual screening
  • CADD
  • FBDD
HTSkeyboard_arrow_down
  • μHTS・HT-MS・TSA
  • Genetic editing technology
  • Compound management
Scaffold Discoverykeyboard_arrow_down
  • Chemoinformatics
  • Parallel synthesis
Natural Product Discoverykeyboard_arrow_down
  • Microorganism library
  • Natural products
"Create" Molecules Essential for Drug Discovery Research

We prepare a wide variety of molecules for use in various evaluations, including new drug candidates, peripheral compounds, and target proteins. For small molecule compounds, we utilize platforms such as parallel synthesis to efficiently synthesize multiple samples, chemical synthesis on the mg-kg scale, and microbial transformation using the molecular transformation capabilities characteristic of microorganisms. For recombinant proteins and antibodies, we use our unique design and production platform to quickly obtain high-quality samples as needed to accelerate the entire drug discovery research process. Recombinant proteins and antibodies can be obtained quickly from high-quality samples that meet the needs of researcher by utilizing our original design and production platform and accelerate the overall drug discovery, and research process.

Drug Discovery Research Platforms

Compound Library Synthesiskeyboard_arrow_down
  • Parallel synthesis
  • Pharma Space Library
  • Lab Automation
Compound Synthesiskeyboard_arrow_down
  • Organic Synthesis
  • Microbial Transformation
Recombinant Proteinskeyboard_arrow_down
  • Design / Production
  • Heterologous Expression
  • Purification
"Evaluate" the characteristics of new drug candidates

We efficiently acquire data for early determination of the qualities and potential of candidate compounds as pharmaceutical products. In addition to in vitro bioactivity and pharmacological activity assessment platfoms using imaging technologies and high density, high precision assessment technologies, we also have proprietary physical property, ADME and toxicological evaluation platforms. Using mass spectrometry (MS) imaging and the latest analytical techniques, we have not only low-molecular-weight compounds but also techniques for measuring in vivo behavior of diverse molecules ranging from peptides, nucleic acids, and other various candidate compounds to biomarkers.

Drug Discovery Research Platforms

Physical Property / Kinetics / Toxicity Evaluationkeyboard_arrow_down
  • Physical property / ADMET screening
  • D/P system
  • High-Speed patch clamp assay
  • Integrated data analysis
Bioactivity evaluationkeyboard_arrow_down
  • High-density and high -precision assay
  • Imaging technology
Bioanalysiskeyboard_arrow_down
  • Nucleic acid / peptide / antibody quantitative analysis
  • MS imaging
"Control" technology to deliver new drug candidate compounds to target

It is important to optimize solubility, absorptive, tissue migration, etc. and to deliver the compound to the target site properly in order for the administered compound to exhibit appropriate efficacy in the body. In order to "manipulate" the pharmacokinetics of compounds, we have a pharmaceutical platform to explore the direction of drug development, and we utilize various technologies to improve oral absorption and control release. We are also focusing on developing new targeting technologies that target the central nervous system and tumors.

Drug Discovery Research Platforms

Exploratory Formulationkeyboard_arrow_down
  • Enhanced oral absorption
  • Controlled release
  • Targeting

Drug Discovery Research Platforms

Structure-Based Drug Design
Contributing to drug discovery through molecular design for various modalities including middle molecule / protein drugs, with a focus on small molecule drugs
構造化学
X-ray crystallography of proteins and compounds
Nakao, N. et al. Communications Chemistry 2, 20(2019)
  • Using the structural analysis of proteins (X-ray crystallography, cryoelectron microscopy), physicochemical methods (NMR, SPR, MST), and computational chemistry, we promote SBDD research from the creation of lead compounds to optimization research.
  • Incorporating state-of-the-art artificial intelligence technologies and cryoelectron microscopy technologies and utilizing biophysics and x-ray crystallography information enables efficient molecular design through virtual screening / CADD. We utilize an original approach that includes FBDD using 19F-NMR and deep learning.

Core Technologies

Structural analysis of proteins / Biophysics / Virtual screening / CADD / FBDD

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Drug Discovery Research Platforms

HTS High-troughput Screening
Acquisition of true hit compounds through high quality HTS utilizing micronization technology and advanced detection technology
HTC
HT-MS (MALDI-TOF MS) system centered on rapipleX (Bruker)
  • To evaluate compounds on a scale of tens to millions, we use high-density microplates of more than 1536 wells. Compared with 96 wells, it reduces materials to about 1/20 and achieves a dramatic improvement in the speed of measurement processing. With the use of equipment capable of ultra-micro dispensing and sensitive measurement of 1μL or less, miniaturization of assay systems and further contrivance for obtaining high-precision data allow uHTS using more than 1 million compound libraries.
  • The HT-MS supports over 1536 wells of high-density microplates, allowing more than 100,000 samples of HT-MS to be screened per day. Highly reliable compound management based on experience including regulatory compliance and cell construction technologies with high-speed, highly precise gene editing support high quality HTS. Making use of advanced HTS functions, we are contributing to the promotion of the DISC project of the Japan Agency for Medical Research and Development (AMED).

Core Technologies

μHTS / HT-MS / TSA / Genetic editing technology / Compound management

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Drug Discovery Research Platforms

Scaffold Discovery
Rapidly acquiring the information and compounds required for hit to lead
HTC
3D pharmacophore fingerprint
  • Making use of chemoinformatics technologies and parallel synthesis platforms, we efficiently expand the SAR of hit compounds (hit expansion), rapidly identifying promising scaffolds.
  • Proprietary 3D pharmacophore fingerprint clustering enables the acquisition of more objective and diverse compound groups. Hit expansion reveals the qualities of the scaffold even with minimal information on the hit compound.

Core Technologies

Chemoinformatics / Parallel synthesis

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Drug Discovery Research Platforms

Natural Product Discovery
Proposing novel natural substance drug discovery
HTC
Muraminomicins
Fujita Y. et al. J Antibiot. 64, 7 495-501(2011)
  • Our microorganism library boasts one of the most diverse and extensive collections in Japan. Various screenings are performed unique to natural products such as HTS and phenotype screening using cultured extract samples created based on proprietary know-how.
  • Bioactive samples are acquired from the hit samples using mass culture, purification, and structural determination techniques. Biosynthetic gene research is also performed on the active substances obtained.

Core Technologies

Microorganism library / Natural products

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Drug Discovery Research Platforms

Compound Library Synthesis
Creation of a new library for PPI drug discovery
HTC HTC
  • By utilizing a platform that combines parallel synthesis technology and high-throughput purification technology, we are able to synthesize 14,000 compounds per year. To date, we have synthesized a library consisting of 100,000 compounds in-house.
  • Practical library design technology based on Pharma Space theory is one of our strengths.

Core Technologies

Parallel synthesis / Pharma Space Library / Lab Automation

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Drug Discovery Research Platforms

Compound Synthesis
Resolving various synthesis needs with powerful technologies
HTC
  • Compounds required for various pharmacological and safety evaluations are synthesized on various scales ranging from mg to kg. Compounds to be synthesized include not only hits found in HTS and small molecule compounds around them, but also natural products, nucleic acids (monomeric derivatives), peptides, TPDs, macrocycles, sugar chains, and probes for target discovery.
  • Microbial transformation technology is also used for compounds that are difficult to obtain by normal chemical synthesis. Especially, there is the synthetic experience of metabolites in the body of drugs, which is essential for safety evaluation.

Core Technologies

Organic Synthesis / Microbial Transformation

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Drug Discovery Research Platforms

Recombinant Proteins
Design and production of fit-for-purpose recombinant proteins
HTC
Constant-temperature incubator
  • We design fit-for-purpose proteins suitable for diverse purposes and utilize expression purification platforms to rapidly create recombinant proteins through heterologous expression.
  • In addition to exploratory uses such as HTS, etc., we design and create numerous proteins for crystallization that require the highest level of quality and quantity and antibodies for physical property analysis and safety tests.
  • There is a variety of needs and expertise in preparing proteins optimized for individual applications through user feedback on the produced proteins.
  • Platforms that enable the original design and creation of optimal proteins to meet the needs are the cornerstone of our technologies to promote advanced drug discovery research.

Core Technologies

Design / Production / Heterologous Expression / Purification

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Drug Discovery Research Platforms

Physical Property / Kinetics / Toxicity Evaluation
Contributing to the acquisition of compounds suitable for drugs through accurate pharmaceutical quality assessment using in vitro data.
HTC
Automated cell culture system
HTC
An example HT-ADMET System: SyncroPatch 384PE (Nanion Technologies GmbH)
  • Characteristics of drug candidate compounds are rapidly and multidimensionally assessed using the physical property, ADME, and toxicities assessment platform. Leveraging the latest automation technologies and multiple newly developed technologies, we rapidly and seamlessly assess physical properties, in vivo pharmacokinetics, and toxicity from a small amount of compound solution. With the highest caliber patch clamp technology in Japan, we conduct highly precise human cardiotoxicity risk assessment.
  • Through high-order physical property evaluation, we assess the development potential of candidate compounds. Based on extensive experience, we provide developmental risk assessments and suggestions for avoidance measures based on physical properties data. Utilizing our own D/P system, we predict the human absorption rate of poorly soluble compounds.

Core Technologies

Physical property / ADMET screening / D/P system / High-Speed patch clamp assay / Integrated data analysis

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Drug Discovery Research Platforms

Bioactivity evaluation
Acquisition of highly precise data for the selection of new drug candidate compounds
HTC
CellVoyager 7000S(Yokogawa Electric Corporation)
  • The biological activity of hit compounds found by methods such as HTS and SBDD/FBDD is evaluated by various methods, and data required for the selection of development candidates are obtained.
  • In the self-free assay, assay systems are constructed under the condition that the compound exerts the effect, and in the cell-based assay, surrogate markers reflecting the disease state are measured with high accuracy.
  • Through the use of imaging technologies, we have a wealth of applications including live imaging, 3D imaging, phenotype texture analysis, and quantification through machine learning.

Core Technologies

High-density and high -precision assay / Imaging technology

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Drug Discovery Research Platforms

Bioanalysis
Pharmacokinetic / biomarker assessment using state-of-the-art analytical techniques
HTC
MS imaging: Intra-renal localization of antibiotics (red)
  • The concentration of the administered compound in the tissues is measured quickly. It also evaluates the intra-organ localization in microregions with MS imaging. In addition, we develop a quantitative method to measure endogenous biomarkers with high accuracy, which contributes to the evaluation of drug efficacy and toxicity of candidate drugs.
  • The analysis of MS and LBA is focused on measuring not only small molecules but also medium molecules, peptides, proteins, nucleic acids, antibodies, and other modalities without labeling compounds.

Core Technologies

Nucleic acid / peptide / antibody quantitative analysis / MS imaging

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Drug Discovery Research Platforms

Exploratory Formulation
A frontrunner in physical property / formulation research in the exploratory stage
HTC
PLGA particles created with microfluidic technology
  • At the exploratory stage, where drug substance provide is limited, we explore the direction of formulation development in accordance with the characteristics of the drug substance, matching candidate compounds from various multi-modalities with formulation technologies and techniques.
  • We are working to provide products that maximize the potential of candidate compounds by leveraging our exploratory drug product platform, which consists of three major DDS technologies (oral absorption improvement, release control, and targeting).
  • In order to adapt to diversifying drug discovery trends, we are challenging the fields of new modalities.

Core Technologies

Enhanced oral absorption / Controlled release / Targeting

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