Presentation on theme: "Development of a web-based compound database system at TEIJIN Pharma: Integration of the compound database and other existing systems TEIJIN PHARMA LIMITED."— Presentation transcript:
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, Teijins 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. About TEIJIN Group
Teijin Group President &CEO Toru Nagashima 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 Organization of the Teijin Group (as of October, 2003)
Pharmaceutical Products In House Products Indication OnealfaAlfacalcidol (1αOHVD 3 )Osteoporosis, Renal Bone Disease BonalfaTacalcitol (1α,24(OH) 2 VD 3 )Psoriasis (Ointment, Cream, Lotion and High conc. ointment) VenilonSulfonated γ-globulinSevere Infectious Diseases Kawasaki Disease Idiopathic Thrombocytopenic Purpura Guillain-Barre Syndrome Anact CActivated Protein CProtein C Deficiency RhinocortSteroid Powder Spray (Nasal)Allergic Rhinitis AftachMucosa Adhesive Steroid Tablet (Mouth) Aphthous Stomatitis SalcoatSteroid Powder Spray (Mouth)Diffuse Aphthous Stomatitis AntupISDN PatchAngina Pectoris
License-in Pharmaceutical Products ProductsIndication Products from B. Ingelheim LaxoberonSodium PicosulfateLaxative Atrovent HFAIpratropium BromideAsthma, COPD MucosolvanAmbroxole HClExpectorant SpiropentClenbuterol HClAsthma, Urinary Incontinence Product from Merck (Gentili) TeirocAlendronate, ivHypercalcemia of Malignancy BonalonAlendronate, poOsteoporosis Product from Fresenius SalivehtArtificial SalivaDry Mouth Product from KAKETSUKEN BolhealFibrinogen PowderAdhesion/Closure of Tissue Product from Morishita Jintan SolmiranEthyl IcosapentatePeripheral 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 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 Isentris 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
Chemical DB Migration
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 Researcher
The Project Time Line Start of the project Examination of platforms Problems -> Specifications Start of operation Development Introduction Start of development 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 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
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 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
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; JChem
JChem - Architecture SQL Plus / DB aplication Oracle search engine jc_contains JChem Streams Adapter JChem Streams Search Engine JChem Core Cache JChem Server JChem Cartridge Engine index table JChem BaseJChem Cartridge JDBC HTTP
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 ISIS/Base remote DB customized using ISIS/PL Browsing Activity Base Assay / ADME
Network Teijin Pharmas 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 JDBC Server compound DB system Client HTTP JChem Server JChem Base Tomcat JavaStandardizer Oracle JChem Cartridge JavaMarvinSketch MarvinView Internet Explorer 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
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 Researcher DocumentsAnalytic 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!!