Transcript スライド 1 - ChemAxon

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
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.
Organization of the Teijin Group (as of October, 2003)
Teijin Group
President &CEO
Toru Nagashima
TEIJIN FIBERS LIMITED (Textile Fibers)
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
Pharmaceutical Products
In House
Indication
Products
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
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
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)
Why TPM Started Re-building Cheminformatics
system?
Background

Increasing Data in Early Research Stage
•
•

Needs for Efficient Feed-back
•

Speeding-up the work flow cycle
Diversified Researchers are Involved
•

Increasing number of compounds
Wide variety of parameters （eADME、eTox・・・）
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
Accelrys software
Chemistry
Academic software
ISIS/Base
>> JChem （Web Browser）
Accord for Excel
Analytical
Design
Drug Discovery work flow
Data Analysis
HTS
Spotfire
Biology ADMET
ActivityBase
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 Isentris
 Continuity
of support for ISIS/Host was unclear
 Limitation by ISIS/Base（ISIS/PL） development
environment

Separated networks
 TEIJIN global Network（for office
• e-mail, Handling office documents
work）
 Research institute LAN（for laboratory work）
• Cheminformatics、Computational Chemistry
• Laboratory Automation

License costs
 Increasing
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
Researcher
Web browser
Researcher
Web browser
Researcher
Compounds DB
Web browser
Assay DB
The Project Time Line
Start of the project
Start of development
Start of operation
’05.10
’06.04～
’06.10～
TPM: 6 chemists
2 assay
Examination
Infocom: 2 IT
of platforms
User WG
•Structure search
•Development Environment
Problems ->
Specifications
•Work flow analysis
Design
•System structure
•Test
•User Interface
Development
•DB contents
Introduction
2006/10 New system started
•Data migration
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：
Accord：
StructureBase：
ChemOffice：
Isentris：
ChemAxon
Accerlys
IDBS
CambridgeSoft
MDL
Platform Examination

Requirement
•
•
•
•
•

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
Why JChem?

Advantages of JChem
•
Affinity with web technology


•
Sufficient basic functions




•
Java
(Future) handling of more diverse data source
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
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
JChem Server
Oracle
JChem Streams Adapter
search engine
JChem Cartridge
⑦
JChem Cartridge Engine
HTTP
JChem Streams
①
⑥
②
JChem Base
Search Engine
③
④
JDBC
jc_contains
・
・
・
Cache
Cache
JChem Core
index table
index table
⑤
Integration of Aplications

DB contents
•
In house compound DB


ISIS/Base remote DB customized using ISIS/PL
Registration of synthesized compounds, corporate ID
generation
•
•
Stock reagent DB

ISIS/Base remote DB customized using ISIS/PL
•
•
main fields： corporate ID, project name, Lot No., purity,
synthetic method etc
main fields： container ID, supplier, catalog No., stocked place,
user etc
Abase Browser


ISIS/Base remote DB customized using ISIS/PL
Browsing Activity Base（Assay / ADME）
Network
ISIS/Base
File Server
-> Web Browser
ActivityBase
SpotFire Server
Documents
Analysis files
Accord for Excel
ChemOffice
Teijin Pharma’s Lab Network
ISIS/Host Server
Accelrys software
-> Web Server
Academic software
Oracle Server
ISIS Database -> JChem Database
ActivityBase Database
Spotfire Database
Work Flow
Accelrys software
Chemistry
Academic software
ISIS/Base
->JChem （Web Browser）
Accord for Excel
Analytical
Design
Drug Discovery work flow
Data Analysis
HTS
Spotfire
Biology ADMET
ActivityBase
System
Server
compound DB system
JChem Server
Client
Standardizer
Java
MarvinSketch
MarvinView
Java
JChem Base
Internet Explorer
Tomcat
HTTP
JDBC
JDBC
Oracle
JChem Cartridge
HTTP
TELI - TEIJIN PHARMA Laboratory Informatics System
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”.
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
View Structure In Table
Structure search
Structure Viewer
File Exporting
Future Plan

Taking advantage of the Web based system・・・
•
Seamless integration with various data sources




•
Easy access to data → More efficient data feed-back!!


Cross-database-search by structure / keyword
Additional functions using JChem（Marvin） features
•

Chemometric descriptors
Analytic data
Link to non-uniform data(ex. in vivo experiment result)
Documents, reports
Highlighting structures, Alignment, Clustering
Development of new tools which works on other
platforms
•
Structure handling from MSOffice(Excel, Word...)
Future Plan
Manager
Web browser
Project Leader
Web browser
Researcher
Web browser
Researcher
Web browser
Researcher
Compound DB
Web browser
Assay DB
Documents
Analytic Data
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!!