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In silico platform for pharmacogenomics “COSMOS” Bio · In silico platform for pharmacogenomics...

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TOKYO UNIVERSITY OF SCIENCE University Research Administration Center 1-3, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan E-MAIL: [email protected] Bio 2019.03 In silico platform for pharmacogenomics “COSMOS” In silico platform for pharmacogenomics “COSMOS” Purpose of Research “Personalized medicine” based on disease genomic big data analysis is anticipated for genome medicine in the twenty-first century. To make this a reality, it is essential to establish a platform for “personalized drug discovery” based on a novel drug discovery methodology that allows molecular design of optimal pharmaceutical lead compounds against disease target molecules in individuals. Currently, the conventional drug discovery method of high-throughput screening of combinatorial chemistry (HTS/CC) conducted in many pharmaceutical companies requires enormous amounts of work, time, and cost; however, in reality, it has a low success rate. To radically change this situation, we have established a novel in silico genome-based drug discovery system “COSMOS” and are conducting research to achieve higher success rates in drug discovery. We have developed a novel drug discovery methodology implementation system, the COSMOS method, targeting protein-protein interactions, which are considered to be difficult to target by conventional drug discovery methods. The concept is to identify an optimal binding peptide that interacts with the active/regulatory site (Hot Spot) of the target drug discovery protein by using in silico methods. Using this as a design element, transformation design to small molecule and automatic optimization is possible by refining the unique binding 3D coordinates. Summary of Research Novel Drug Discovery Strategy Targeting Protein-Protein Interactions Target protein Optimal binding peptide (Design element) Peptide Docking Study Optimal drug molecule Mimetic compound Seed compound Optimal lead compound Peptide library (20 n –300 n ) Small-molecule compound library (Up to 5 × 10 6 ) Future Developments Validation of the applicability of COSMOS method and discovery of novel lead compounds will be done in collaboration with pharmaceutical companies to develop novel drugs. Associated System: Grants-in-Aid for Scientific Research 2015 Basic Research (C) 2016 Basic Research (B) Intellectual Property: Japanese Patent No. 4612270 “Design method and applications for physiologically-active peptides” Highly experienced in collaborative research with companies Sei-ichi TANUMA (Professor, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science) Ryoko TAKASAWA (Junior Associate Professor, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science) Akira SATO (Junior Associate Professor, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science) Optimal peptide
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Page 1: In silico platform for pharmacogenomics “COSMOS” Bio · In silico platform for pharmacogenomics “COSMOS”In silico platform for pharmacogenomics “COSMOS” Purpose of Research

TOKYO UNIVERSITY OF SCIENCE University Research Administration Center

1-3, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan E-MAIL: [email protected]

Bio

2019.03

In silico platform for pharmacogenomics “COSMOS”In silico platform for pharmacogenomics “COSMOS”

Purpose of Research

“Personalized medicine” based on disease genomic big data analysis is anticipated for genome medicine in the twenty-first century. To make this a reality, it is essential to establish a platform for “personalized drug discovery” based on a novel drug discovery methodology that allows molecular design of optimal pharmaceutical lead compounds against disease target molecules in individuals. Currently, the conventional drug discovery method of high-throughput screening of combinatorial chemistry (HTS/CC) conducted in many pharmaceutical companies requires enormous amounts of work, time, and cost; however, in reality, it has a low success rate. To radically change this situation, we have established a novel in silico genome-based drug discovery system “COSMOS” and are conducting research to achieve higher success rates in drug discovery.

We have developed a novel drug discovery methodology implementation system, the COSMOS method, targeting protein-protein interactions, which are considered to be difficult to target by conventional drug discovery methods. The concept is to identify an optimal binding peptide that interacts with the active/regulatory site (Hot Spot) of the target drug discovery protein by using in silico methods. Using this as a design element, transformation design to small molecule and automatic optimization is possible by refining the unique binding 3D coordinates.

Summary of Research

Novel Drug Discovery Strategy Targeting Protein-Protein Interactions

Target proteinOptimal binding peptide

(Design element)

Peptide Docking

Study

Optimal drug molecule

Mimetic compound

Seed compound

Optimal lead compound

Peptide library(20n–300n)

Small-molecule compound library

(Up to 5 × 106)

Future Developments

Validation of the applicability of COSMOS method and discovery of novel lead compounds will be done in collaboration with pharmaceutical companies to develop novel drugs.

Associated System: Grants-in-Aid for Scientific Research2015 Basic Research (C)2016 Basic Research (B)

Intellectual Property: Japanese Patent No. 4612270 “Design method and applications for physiologically-active peptides”

Highly experienced in collaborative research with companies

Sei-ichi TANUMA (Professor, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science)Ryoko TAKASAWA (Junior Associate Professor, Department of Pharmacy, Faculty of Pharmaceutical Sciences,

Tokyo University of Science)Akira SATO (Junior Associate Professor, Department of Pharmacy, Faculty of Pharmaceutical Sciences,

Tokyo University of Science)

Optimal peptide

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