Development of a web-based compound database system at TEIJIN Pharma: Integration of the compound database and other existing systems

Development of a web-based compound database system at TEIJIN Pharma: Integration of the compound database and other existing systems

TEIJIN PHARMA LIMITED

Sogawa Ryo (Medicinal Chemist)

14 June, 2007

TEIJIN PHARMA LIMITED

Sogawa Ryo (Medicinal Chemist)

14 June, 2007

Teijin Limited, established in 1918, was the first Japanese company to produce rayon, and has remained an innovator and leader in the development and commercialization of fibers.

Since then, Teijin has capitalized on its expertise in fibers to diversify into other fields.

Today, Teijin’s operations encompass four segments: 1. Fibers and Textiles2. Films and Plastics3. Pharmaceuticals and Home Health Care4. Newly Developed Businesses

At present, Teijin is utilizing its proprietary technologies to expand into promising new areas, notably health-care products and services, advanced materials and information media.

About TEIJIN Group

Teijin GroupPresident &CEO

Toru Nagashima

Teijin GroupPresident &CEO

Toru Nagashima

TEIJIN FIBERS LIMITED (Textile Fibers)TEIJIN FIBERS LIMITED (Textile Fibers)

TEIJIN TECHNO PRODUCTS LIMITED (Industrial Fibers)TEIJIN TECHNO PRODUCTS LIMITED (Industrial Fibers)

NI TEIJIN SHOJI CO., LTD. (Fiber Products Marketing)NI TEIJIN SHOJI CO., LTD. (Fiber Products Marketing)

TEIJIN FILMS LIMITED, TEIJIN DUPONT FILM GLOBALJVS (Film)

TEIJIN FILMS LIMITED, TEIJIN DUPONT FILM GLOBALJVS (Film)

TEIJIN CHEMICALS LIMITED (Plastics)TEIJIN CHEMICALS LIMITED (Plastics)

TEIJIN PHARMA LIMITED TEIJIN PHARMA LIMITED

Pharmaceutical Business Unit & Home Healthcare Business Unit

INFOCOM CORPORATION (IT Business)INFOCOM CORPORATION (IT Business)

New Business Development Business GroupNew Business Development Business Group

Organization of the Teijin Group (as of October, 2003)

Pharmaceutical Products

In House

ProductsIndication

Onealfa Alfacalcidol (1αOHVD3) Osteoporosis, Renal Bone Disease

Bonalfa Tacalcitol (1α,24(OH)2VD3) Psoriasis (Ointment, Cream, Lotion and High conc. ointment)

Venilon Sulfonated γ-globulin Severe Infectious Diseases

Kawasaki Disease

Idiopathic Thrombocytopenic Purpura

Guillain-Barre Syndrome

Anact C Activated Protein C Protein C Deficiency

Rhinocort Steroid Powder Spray (Nasal) Allergic Rhinitis

Aftach Mucosa Adhesive Steroid Tablet (Mouth)

Aphthous Stomatitis

Salcoat Steroid Powder Spray (Mouth) Diffuse Aphthous Stomatitis

Antup ISDN Patch Angina Pectoris

License-in

Pharmaceutical Products

Products Indication

Products from B. Ingelheim

Laxoberon Sodium Picosulfate Laxative

Atrovent HFA Ipratropium Bromide Asthma, COPD

Mucosolvan Ambroxole HCl Expectorant

Spiropent Clenbuterol HCl Asthma, Urinary Incontinence

Product from Merck (Gentili)

Teiroc Alendronate, iv Hypercalcemia of Malignancy

Bonalon Alendronate, po Osteoporosis

Product from Fresenius

Saliveht Artificial Saliva Dry Mouth

Product from KAKETSUKEN

Bolheal Fibrinogen Powder Adhesion/Closure of Tissue

Product from Morishita Jintan

Solmiran Ethyl Icosapentate Peripheral Arterial Disease

Research & Development

•R&D Investment15% of the turnover

•Research Institute: Founded in 1974 at Hino-city, Tokyo

GLP Safety Evaluation Center (1982)New Pharmacological Research Center (1994)New Pharmacokinetic Research Center (1998)New Pharmaceutical Research Center (1998)ca. 300 Researchers

•Clinical DevelopmentTokyo Office, ca 80 staffTeijin America, Inc. (Princeton, NJ, USA)

Why TPM Started Re-building Cheminformatics system?

Background

Increasing Data in Early Research Stage• Increasing number of compounds• Wide variety of parameters （ eADME 、 eTox ・・・）

Needs for Efficient Feed-back• Speeding-up the work flow cycle

Diversified Researchers are Involved• Researchers with diversified background

Various Data in Various Formats• Biological activity, ADME, Safety, ...• Excel, Oracle DB, Word document...

Increasing Numbers of Compounds

10 times increase in 10 years

Clear contribution of combinatorial chemistry (red in figure)

Wide Variety of Parameters

Increasing number of parameters from “wet” experiment• Optimization of one parameter (activity)

Simultaneous optimization of multiple parameters Computational parameters

• Tens of chemical descriptors are available for SAR analysis

The size of data researchers have to consider is

(#compounds) x (#parameters)!!

Work Flow Cycle

Design

Chemistry

Analytical

HTS

Biology ADMET

Data Analysis

Accord for Excel

ISIS/Base

ActivityBase

Spotfire

Accelrys software

Academic software

Drug Discovery work flow

>> JChem （ Web Browser ）

Requests to Cheminformatics Tools (from Researchers)

Interactive browsing and analysis on multiple compounds/parameters information

Stable handling of huge data Easy registration and access to various data source

• No special skill needed Satisfy different needs of researchers of different

background

Problems

Platform migration from ISIS to IsentrisContinuity of support for ISIS/Host was unclearLimitation by ISIS/Base （ ISIS/PL ） developmen

t environment

Separated networksTEIJIN global Network （ for office work ）

• e-mail, Handling office documentsResearch institute LAN （ for laboratory work ）

• Cheminformatics 、 Computational Chemistry• Laboratory Automation

License costsIncreasing number of named user licenses

Chemical DB Migration

Aim

Aim• Re-building of compounds DB system without ISIS

ISIS 　→　？？？• Data can be registered/browsed from individual clients for each

researcher in various sections Migration to Web-based compound DB system

Compounds DB

Assay DB

Web browser

Web browser

Web browser

Researcher

Researcher

Researcher

The Project Time Line

Start of the project

’05.10

Examination

of platforms

Problems ->

Specifications

Start of operation

’06.10～

Development

Introduction

Start of development

’06.04～

Design

2006/10 New system started

User WG

TPM: 6 chemists

2 assay

Infocom: 2 IT

•Structure search

•Development Environment

•Work flow analysis

•System structure

•User Interface

•DB contents

•Test

•Data migration

Platform Examination

To which platform should we migrate?• Structure search function ？ →　 speed 、 accur

acyThe system must precisely recognize various complex chemi

cal structures!!

• Development environment ？→　 language 、 OS• Candidates

JChem ： ChemAxonAccord ： AccerlysStructureBase ： IDBSChemOffice ： CambridgeSoft Isentris ： MDL

Platform Examination

Requirement• Improvement of user accessibility → 　 Web based system• Integration of aplications → 　 Structure search w

ith SQL• Uniform user interface → 　 Chemical editor• Management of all in house compounds→ 　 Precise structure h

andling• Low cost

Candidates JChem ： ChemAxon Accord ： Accerlys StructureBase ： IDBS ChemOffice ： CambridgeSoft Isentris ： MDL

Why JChem?

Advantages of JChem• Affinity with web technology

Java (Future) handling of more diverse data source

• Sufficient basic functionssubstructure and similarity searching inserting and modifying data in structure tablesmanipulating structuresSDfile, Molfile, SMILES import/export

• Chemical editorMarvinSketch : for structure input and modificationMarvinView : for displaying structures

JChem - Chemistry Engine

JChem• JChem Base

JDBC Structure search with Java Class 　→　 Searchable in many DBs

（ Oracle, MySQL, MSSQL Server, MS Access, DB2, PostgreSQL etc… ）

JChemSearch searcher = new chemaxon.jchem.db.JChemSearch();searcher.setConnectionHandler(ch);searcher.setSearchType(JChemSearch.SUBSTRUCTURE)searcher.setQueryStructure(“c1ccccc1”);searcher.setStructureTable(“SCOTT.STRUCTURES”);searcher.run();int[] results=searcher.getResults();

• JChem Cartridge for Oracle Oracle data cartridge Structure search with SQL 　→　 Non- Java environment is possible

（ VB, VC++, .NET etc… ）SELECT cd_id FROM scott.jchemtable WHERE jc_contains(smiles, 'CN1C=NC2=C1C(=O)N(C)C(=

O)N2C') = 1;

情報参照先 JChem http://www.chemaxon.com/jchem/

JChem - Architecture

SQL Plus / DB aplication

Oracle

search engine

jc_contains

JC

he

m S

tream

s A

da

pte

r

JChem Streams

Search Engine

JChem Core

Cache

Cache

JChem Server

JChem Cartridge Engine

index table index table

JChem BaseJChem Cartridge

JDBC

HTTP

・・・

①②

③ ④⑤

⑥

⑦

Integration of Aplications

DB contents• In house compound DB

ISIS/Base remote DB customized using ISIS/PLRegistration of synthesized compounds, corporate ID

generation• main fields ： corporate ID, project name, Lot No., purity,

synthetic method etc

• Stock reagent DB ISIS/Base remote DB customized using ISIS/PL

• main fields ： container ID, supplier, catalog No., stocked place, user etc

• Abase Browser ISIS/Base remote DB customized using ISIS/PLBrowsing Activity Base （ Assay / ADME ）

Network

Teijin Pharma’s Lab Network

ISIS/Host Server

Oracle Server

ISIS Database

ActivityBase Database

SpotFire Server

Accelrys software

Academic software

ISIS/Base

ActivityBase

Accord for Excel

ChemOffice

File Server

Spotfire Database

Documents

Analysis files

-> Web Server

Oracle Server

-> JChem Database

-> Web Browser

ActivityBase

Accord for Excel

ChemOffice

Work Flow

Design

Chemistry

Analytical

HTS

Biology ADMET

Data Analysis

Accord for Excel

ISIS/Base

ActivityBase

Spotfire

Accelrys software

Academic software

Drug Discovery work flow

->JChem （ Web Browser ）

System

JDBCJDBC

Server

compound DB system Client

HTTP

JChem Server

JChem Base

Tomcat

JavaStandardizer

OracleJChem Cartridge

Java MarvinSketchMarvinView

Internet Explorer

HTTP

TELI - TEIJIN PHARMA Laboratory Informatics System

TELITEIJIN PHARMA Laboratory Informatics System

Cheminformatics technologies (mainly chemical DB) has been successfully applied to medicinal chemistry research. As a next step, we are planning to introduce and establish “Laboratory Informatics” technology, which enables us to directly handle “wet” data from various experiments. This system development is the start point of such an approach, and we named this system using the words, “Laboratory Informatics System”.

TELI - TEIJIN PHARMA Laboratory Informatics System

TELI - TEIJIN PHARMA Laboratory Informatics System

TELI - TEIJIN PHARMA Laboratory Informatics System

Spotfire Modules for JChem

Spotfire Modules for JChem• An application using Chemistry Framework

Data Provider （ DB connecting module ）• Link to the structure data (.mol format) from Spotfire Server• Integration of structural data and non-structural data• Structure search from Spotfire• Pick up the search result from Spotfire

Structure Renderer （ Structure drawing module ）• Exchange structure data into EMF （ Enhanced Meta File)• Display on screen

Spotfire Modules for JChem

Structure Viewer

View Structure In Table

Structure search

File Exporting

Future Plan

Taking advantage of the Web based system ・・・• Seamless integration with various data sources

Chemometric descriptors Analytic data Link to non-uniform data(ex. in vivo experiment result) Documents, reports

• Easy access to data 　→　 More efficient data feed-back!! Cross-database-search by structure / keyword

Additional functions using JChem （ Marvin ） features• Highlighting structures, Alignment, Clustering

Development of new tools which works on other platforms

• Structure handling from MSOffice(Excel, Word...)

Future Plan

Compound DB

Assay DB

Web browser

Web browser

Web browser

Researcher

Researcher

Researcher

Documents Analytic Data

Web browser

Manager

Web browser

Project Leader

Conclusion

Client/Server -> Web based application • Improvement of accessibility• Easy user interface• Decrease maintenance costs

In-house development• Optimized for in-house workflow• Future development

We are moving into next generation!!