1. TEIJIN PHARMA LIMITED Sogawa Ryo (Medicinal Chemist) 14 June, 2007
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

2. About TEIJIN Group
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 Textiles
2. Films and Plastics
3. Pharmaceuticals and Home Health Care
4. 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.

3. Organization of the Teijin Group (as of October, 2003)
TEIJIN FIBERS LIMITED (Textile Fibers)
Teijin Group
President &CEO
Toru Nagashima
TEIJIN TECHNO PRODUCTS LIMITED (Industrial Fibers)
NI TEIJIN SHOJI CO., LTD. (Fiber Products Marketing)
TEIJIN FILMS LIMITED, TEIJIN DUPONT FILM GLOBALJVS (Film)
TEIJIN CHEMICALS LIMITED (Plastics)
TEIJIN PHARMA LIMITED
Pharmaceutical Business Unit & Home Healthcare Business Unit
INFOCOM CORPORATION (IT Business)
New Business Development Business Group

4. Pharmaceutical Products
In House
Products
Indication
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

5. Pharmaceutical Products
License-in
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

6. Research & Development
R&D Investment
15% 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 Development
Tokyo Office, ca 80 staff
Teijin America, Inc. (Princeton, NJ, USA)

7. Why TPM Started Re-building Cheminformatics system?

8. Increasing Data in Early Research Stage
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...

9. Increasing Numbers of Compounds
10 times increase in 10 years
Clear contribution of combinatorial chemistry (red in figure)

10. 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)!!

11. Work Flow Cycle Drug Discovery work flow Chemistry Accelrys software
Academic software
ISIS/Base
>> JChem （Web Browser）
Accord for Excel
Design
Analytical
Drug Discovery work flow
Data Analysis
HTS
Spotfire
Biology ADMET
ActivityBase

12. 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

13. Problems Platform migration from ISIS to Isentris Separated networks
Continuity of support for ISIS/Host was unclear
Limitation by ISIS/Base（ISIS/PL） development environment
Separated networks
TEIJIN global Network（for office work）
, Handling office documents
Research institute LAN（for laboratory work）
Cheminformatics、Computational Chemistry
Laboratory Automation
License costs
Increasing number of named user licenses

14. Chemical DB Migration

15. Aim Aim Re-building of compounds DB system without 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
Researcher

16. The Project Time Line 2006/10 New system started Start of the project
’05.10
Start of development
’06.04～
Start of operation
’06.10～
TPM: 6 chemists
2 assay
Infocom: 2 IT
Examination
of platforms
User WG
Problems ->
Specifications
Structure search
Development Environment
Design
Work flow analysis
System structure
Test
Data migration
Development
Introduction
User Interface
DB contents
2006/10 New system started

17. Platform Examination To which platform should we migrate?
Structure search function？ →　speed、accuracy
The system must precisely recognize various complex chemical structures!!
Development environment？→　language、OS
Candidates
JChem： ChemAxon
Accord： Accerlys
StructureBase： IDBS
ChemOffice： CambridgeSoft
Isentris： MDL

18. Platform Examination Requirement Candidates
Improvement of user accessibility →　Web based system
Integration of aplications →　Structure search with SQL
Uniform user interface →　Chemical editor
Management of all in house compounds→　Precise structure handling
Low cost
Candidates
JChem： ChemAxon
Accord： Accerlys
StructureBase： IDBS
ChemOffice： CambridgeSoft
Isentris： MDL

19. Why JChem? Advantages of JChem Affinity with web technology
Java
(Future) handling of more diverse data source
Sufficient basic functions
substructure and similarity searching
inserting and modifying data in structure tables
manipulating structures
SDfile, Molfile, SMILES import/export
Chemical editor
MarvinSketch : for structure input and modification
MarvinView : for displaying structures

20. JChem - Chemistry Engine
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

21. SQL Plus / DB aplication JChem Cartridge Engine
JChem - Architecture
SQL Plus / DB aplication
JChem Server
Oracle
JChem Streams Adapter
HTTP
JChem Streams
search engine ① ⑥ ②
JChem Cartridge
JChem Base ⑦
JChem Cartridge Engine
Search Engine ③ ④
jc_contains
JDBC
Cache ⑤
・・・
Cache
JChem Core
index table
index table

22. Integration of Aplications
DB contents
In house compound DB
ISIS/Base remote DB customized using ISIS/PL
Registration 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
Browsing Activity Base（Assay / ADME）

23. Network -> Web Browser ActivityBase Accord for Excel ChemOffice
ISIS/Base
ActivityBase
Accord for Excel
ChemOffice
File Server
SpotFire Server
Documents
Analysis files
Teijin Pharma’s Lab Network
-> Web Server
Oracle Server
ISIS/Host Server
Oracle Server
Accelrys software
Academic software
ISIS Database
-> JChem Database
ActivityBase Database
Spotfire Database

24. Work Flow Drug Discovery work flow Chemistry ->JChem （Web Browser）
Accelrys software
Academic software
ISIS/Base
Accord for Excel
Design
Analytical
Drug Discovery work flow
Data Analysis
HTS
Spotfire
Biology ADMET
ActivityBase

25. System Server Client compound DB system JChem Server Standardizer Java
MarvinSketch
MarvinView
JChem Base
Internet Explorer
Tomcat
HTTP
JDBC
JDBC
HTTP
Oracle
JChem Cartridge

26. TELI - TEIJIN 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”.

27. TELI - TEIJIN PHARMA Laboratory Informatics System

28. TELI - TEIJIN PHARMA Laboratory Informatics System

29. TELI - TEIJIN PHARMA Laboratory Informatics System

30. 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

31. Spotfire Modules for JChem
View Structure In Table
Structure search
Structure Viewer
File Exporting

32. 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...)

33. Future Plan Manager Web browser Project Leader Web browser Researcher
Compound DB
Web browser
Assay DB
Analytic Data
Documents

34. We are moving into next generation!!
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!!