lsevier MDL and GeneGo havelinked databases to make it easierand quicker for researchers to

access more information without repeatingsearches in multiple diverse platforms. TheGeneGo databases for systems biologyand pathway analysis (MetaCore™ andMetaDrug™) are now linked with thesynthesis, sourcing and bioactivity data-bases on the DiscoveryGate® platform.

MetaCore is a unique, curated databaseof human protein-protein and protein-DNAinteractions, transcription factors, signalingand metabolic pathways and the effectsof bioactive molecules. MetaDrug is asystems pharmacology platform thatpredicts human drug metabolism, potentialtoxicities and mode of action for novelsmall molecules.

The collaboration enables researchersto identify drug targets and bioactivecompounds via pathway analysis andretrieve comprehensive information ontheir synthesis, biological effects andcommercial availability without having to re-query for it.

“The integration of MDL databases with GeneGo’s pathways informationsystems enables scientists to bridge thegap between cell biology and medicinalchemistry,” says Steve Young, Director of MDL Content Strategy. “For the firsttime, biologists will be able to quicklyreview cheminformatics data of smallmolecules involved in biological pathways,and chemists will be able to view molecularpathway information related to theirlead compounds.”

“Lately, a number of customersapproached us with requests for functional

analysis of the effects of drug-like com-pounds rather than genomic data,” saysJulie Bryant, VP Business Developmentat GeneGo. “Although pathways andnetwork analysis of bioactive compoundsis a common practice in MetaCore, wepartnered with Elsevier MDL for in-depthcoverage of literature- and patent-derivedinformation relevant for compounds. We are very pleased to be working with

Elsevier MDL, the market leader inmedicinal chemistry factual databases.Integration with the Elsevier MDL chemistryspace opens up new applications for our products in medicinal chemistry,including high-throughput and high-content screening, hit selection and validation, lead development programsand chemogenomics.”

Reprint f rom Molecular Connect ion Vol 24 No 4 2006

Collaboration with GeneGo provides seamless access to compound databases,

patents, literature and biological pathways

GeneGo develops systems biology technology for life sciences research. The original computational platform allows an integration and expert analysis of differentkinds of experimental data (mRNA expression, proteomics, metabolomics, siRNA and other phenotypicdata) and relevant bioactive chemistry (metabolites, drugs, other xenobiotics) withinthe framework of curated biological pathways and networks. GeneGo’s flagship product, MetaCore, assists pharmaceutical scientists in the areas of target selectionand validation, identification of biomarkers for disease states and toxicology. MetaDrug is designed for prediction of human metabolism, toxicity and biological effects fornovel small molecules compounds. MetaBase™ represents the knowledge base for MetaCore. For more information about GeneGo products and services, pleasevisit www.genego.com.

About GeneGo

“For the first time, biologists will be able to quickly

review cheminformatics data of small molecules

involved in biological pathways, and chemists will be

able to view molecular pathway information

related to their lead compounds.”

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Reprint f rom Molecular Connect ion Vol 24 No 4 2006

You want to study related pharmaco-

logical information (e.g., adverse effects,

toxicity, dose response curves, primary

literature, etc.) on Celecoxib, a known

COX-2 inhibitor.

In GeneGo you conduct a signaling

networks search on Celecoxib which

builds a network mapping the relation-

ship between this compound and

targets/receptors.

Figure 1: The Celecoxib molecule is shown in the network diagram (purple hexagon, circled).

Double-click on the Celecoxib purplehexagon to open the ‘Chemical compounddetails’ display.

The default search type when transferringa structure to DiscoveryGate is automaticsearch. The system looks for records thatmatch the query using the followingsearch types in this order: exact match,include isomers, include tautomers, includesalts, substructure, similarity (90%) andsimilarity (70%), until at least one hit isfound. Each search is somewhat moregeneral than the preceding search.

Select substructure as the searchmethod to receive all substances thatcontain the Celecoxib core structure andthen click on Search in DiscoveryGateto transfer this structure to the MDL®

Compound Index (license to DiscoveryGaterequired).

In addition to target information fromMetaCore you get pharmacology, safety,toxicity, adverse effort and metabolismdata, as well as commercial availabilityand preparation data via DiscoveryGate.

Select Details on the Celecoxibrecord to see all related records availablevia the Compound Index.

Figure 2: Celecoxib compound details. A reaction in GeneGo nomenclature is equivalent to ametabolic transformation in MDL databases.

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Figure 3: The ‘Grid View’ (background) allows you to quickly see all related structures containingthe Celecoxib core structure. The ‘Properties View’ (foreground) shows related records in a properties context.

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2

The integration of MDL

databases with GeneGo’s

pathways information

systems bridges the gap

between cell biology and

medicinal chemistry.

Reprint f rom Molecular Connect ion Vol 24 No 4 2006

Figure 4: DiscoveryGate provides “Also found in” links at the top of each record offering immediate connections to relevant information on the same compound in other data sources.

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Figure 5: xPharm and PharmaPendium record displays for Celecoxib (xPharm and PharmaPendiumlicenses required).

Figure 6: Information in PubChem is categorized based on the Medical Subject Heading(MeSH) indexing schema.

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This record for Celecoxib includes directlinks to the GeneGo databases, that is,bidirectional linking is enabled (MetaCoreand/or MetaData licenses required).

Click on xPharm® and PharmaPendium™

in the ‘Also found in’ links to access awealth of pharmacological and adverseeffects information on Celecoxib.

Click on PubChem in the ‘Also foundin’ links to access bioassay data.

Select PubMed via MeSH to accessassociated biological and pharmacologicaleffect information from the correspondingprimary literature.

DiscoveryGate and the MDL®

Compound Index

The online DiscoveryGate platform(www.discoverygate.com) providesaccess to integrated scientific con-tent from databases, journal articles,patent publications and referenceworks from information providersincluding Elsevier, Thomson-Derwent,FIZ CHEMIE, the USFDA, ProusScience and Thieme.

With the addition of chemicalstructures from the GeneGo data-bases, MetaCore and MetaDrug, the MDL Compound Index (the master list of substances included in DiscoveryGate data sources) now exceeds 16.5 million uniquechemical structures. Altogether, morethan 22 million unique structures areaccessible via DiscoveryGate.

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The collaboration with

GeneGo expands the network

by enabling researchers to

link from molecules in

GeneGo’s biological

pathways to DiscoveryGate

to find related information.

Indexing third-party data in theCompound Index extends the network

of platforms interlinked via DiscoveryGateand provides researchers with unified,simple access to a wealth of related data.

The GeneGo linking was made possibleby using the ‘Send-To’ mechanism,which enables the transfer of chemicalstructures from in-house or third-partyapplications directly to DiscoveryGatevia a single click in the application.

The chemical structure is convertedto a Chimestring in the GeneGo application via a dynamic molfile-to-Chimestring conversion (using classesin csinline.jar). The researcher selectsthe search type (e.g., automatic, exact,substructure, include stereoisomers,include tautomers and include salts).When the researcher clicks on the trigger point, the Chimestring and thesearch type are placed on a hidden Webform which is sent to DiscoveryGate.

The ‘Send-To’ mechanism can beimplemented in customer proprietaryapplications (COM, .net, Java).

‘Send-To’ mechanism makes GeneGo integration possible

Reprint f rom Molecular Connect ion Vol 24 No 4 2006

MDL, DiscoveryGate and PharmaPendium are registered trademarks or trademarks of MDL Information Systems, Inc. ('Elsevier MDL')in the United States and/or other countries. MetaCore, MetaDrug and MetaBase are trademarks of GeneGo, Inc. xPharm is a registeredtrademark of Elsevier, Inc. in the United States and other countries. ScienceDirect is a registered trademark of Elsevier B.V. All otherproduct and company names mentioned herein may be trademarks or registered trademarks of their respective holders.

Copyright © 2006 Elsevier MDL. All rights reserved.

Elsevier MDL2440 Camino Ramon,Suite 300San Ramon, CA 94583Tel: +1(925) 543-5400Fax: +1(925) 543-5401www.mdl.com

Figure 7: Celecoxib-related citations available in PubMed.

Figure 8: In ScienceDirect, scientists can read and print the published article in its entirety(ScienceDirect license required).

More information

‘Send-To’ mechanism article from Molecular Connection (2005, Vol. 23, No. 3, page 10) and

this article are available as reprints (PDF). www.mdl.com/products/knowledge/discoverygate

See this case study as an interactive video. www.mdl.com/videos

Sign-up for a 30-day trial of DiscoveryGate (no fee, no obligation to buy, subject to acceptance

of the applicable DiscoveryGate Evaluation license). www.discoverygate.com

Read a review article about xPharm®, reprinted from the Journal of Electronic Resources in Medical

Libraries, courtesy of The Haworth Press, Inc. www.mdl.com/products/pdfs/xpharm.pdf

With the addition of chemical structures from

the GeneGo databases, MetaCore and MetaDrug,

the MDL Compound Index now exceeds

16.5 million unique chemical structures.

Select Links > Linkout and ElsevierMDL to access the full article onScienceDirect.

From its inception, DiscoveryGate has

provided researchers with focused informa-

tion, relevant to specific research questions,

from a network of indexed and linked data

sources. As the above scenario shows,

collaboration with GeneGo expands the

network by enabling researchers to link

from molecules in GeneGo’s biological

pathways (a display of networks around

proteins, genes and compounds) to

DiscoveryGate to find related information.

This integration will help researchers

find critical information while avoiding

unnecessary, repetitious searches of

multiple systems or data sources.

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