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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!!