ISIS

Information Systems, Inc.

Delivering a World of Discovery Information

Integrated Scientific Information System

cientists who need robust, versatile, easy-to-use tools in

today’s fast-paced discovery environmentoverwhelmingly choose MDL’s ISIS, the leading informatics system in thelife science and chemical industries.

ISIS is extremely adaptable in sup-porting the data management needs ofindividuals, project teams, and corporateinformation groups, maintaining a consistent look and feelfrom the individual to theenterprise level. Built on adistributed-computing,client-server model, ISISenables scientists to capture and manage data,collaborate with research groups, andsynchronize information with corporatesystems. ISIS also hosts a wide-range ofapplications for exploiting its foundationtechnology. Scientists can work in theirenvironment of choice—MicrosoftExcel, any Web browser, Visual Basic, orISIS/Base. From all of these, ISIS pro-vides a comprehensive, reliable informaticsframework to deliver discovery informa-tion to the desktop. The system’s scalability and breadth of application

support integrates corporate workflow,increases productivity, lowers the cost of distribution—and distinguishes ISISfrom the point solutions offered byother vendors.

Uniquely Suited forData Capture andValidation

ISIS provides enormousflexibility to assist with creating scientific data andis uniquely suited for datacapture and validation.Scientists working on either PCs or

Macintoshes commonly use the systemin a wide range of disciplines, includingchemistry, therapeutic biology, agro-chemical biology, analytical chemistry,metabolism, toxicology, and administra-tion (e.g. in the sample room). MDLtools such as Cheshire for ISIS and theFlexmatch operators combine to provideISIS with the most comprehensive andaccurate chemical structure validationand novelty checking in the industry.

ISIS also supplies the most sophisti-cated tools for editing and registeringchemical structures. The system sets no limits on the size of the molecules,and enables scientists to draw and register small molecules, polymers,proteins, models, reactions, mixtures,and formulations—the largest set ofdata types of any system on the market.

Flexible, ScalableSupport for a World of Discovery Information

Chemistry

SampleInven

Reagents

Lead Identification

Figure 1: Working either out of the box or, as seen here, with a custom data-entry dialog box, ISIS provides the high level of precision needed when registering chemical structures and streamlines theassociation of chemical, biological, or other experimental data with chemical structures or reactions.

"We selected

ISIS because of its

speed, performance, and

flexibility. ISIS enables

us to enhance our

current capabilities, to

manage our chemistry

data using modern

information technology

standards, and to

integrate data seamlessly

with existing applications.

We have very aggressive

productivity goals, and

ISIS will help us manage

the huge amount of

information that results

from our extensive

discovery program."

Dr. Marcel JanssenVice President of Medicinal Chemistry

Janssen Research Foundation

With ISIS, researchers know that whatgoes into a database has been properlyvalidated, and that it is represented withthe precision and accuracy necessary tomeet diverse scientific requirements fromthe individual to the enterprise level.

Integration,Integration,Integration. . .

Integration is the mantra of today’sdiscovery informatics. Yet only recentlyhave RDBMS vendors rushed to supportthe hierarchical data structures thataccommodate sophisticated data-miningand decision-support applications. MDLpioneered the integration of heteroge-neous databases in the life science andchemical industries. In the early 1990sMDL patented a heterogeneous jointechnology to provide scientists withsimple, yet powerful views of integrateddata in a hierarchical context. ISIS

allows researchers to bring together data from diverse sources—chemistry,biology, metabolism, toxicology, etc.—toproduce actionable information thatsupports successful decisions. Scientistscan use integrated data for reportingand for changing the presentation of information, or they can pass it along to sophisticated analysis software suchas MDL’s ISIS for Excel, SAR Table,SCULPT, or Spotfire from Spotfire, Inc.

Unlike other systems, ISIS does notsimply look up small subsets of informa-tion via Open DataBase Connectivity(ODBC) from relational databases. The solution integrates very large

repositories—relational, chemical, etc.—at the server level by establishing a heterogeneous join over many differentdatabase types. This approach allowsscientists to query and explore the entireintegrated database in real time, and toask the questions they need to ask acrossthe discovery enterprise. And the integra-tion potential of ISIS is further enhancedwith the release of ISIS/Direct, MDL’sdata cartridge for Oracle 8i. ISIS/Directworks with desktop chemistry tools fromMDL such as ISIS/Draw, Chime Pro,and ISIS/Object Library, allowing anapplication to send chemically-extendedSQL to the Oracle 8i engine.

Biology

Development

e Roomntory

n and Optimization

Real-Life Data Types

With over 20 years of experiencebuilding decision-support systemsand registration environments, MDLleads the industry in supporting the variety of chemical data typesused in discovery research. Thesearching diagram (left) illustratesthe breadth of chemistry available,with the results diagram (below)providing a glimpse into the types of chemical informationreturned to the user.

Cheminformatics Searching

Cheminformatics Results

A.Biopolymer C.Product NotReactant

D. ReactionTransformation

F. TautomersSearch

I. SubstructureH.ExactStructure

J. Similarity K. PolymerSearching

A.Protein B. 3D Models

E. RgroupD. ReactionTransformation

K. Monomer within CopolymerJ. Similarity

G.AbsoluteStereoisomer I. Substructure

H.ExactStructure

F. Tautomer Hit

C.Ring-Forming Reaction

E. Rgroup

G.Relative/AbsoluteStereoisomer

B. 3D Constraints & ConformationalFlexible Search

Power Tools forDecision Support

The Web and distributed computingenvironments such as ISIS have madethe deployment of business informationeasier than ever. New tools have evolvedto provide effective access to the worldof scientific information and to systemsfor presenting, analyzing, and visualizingthe ever larger sets of discovery data. Thedata presentation, analysis, and visual-ization environments available throughISIS exploit the comprehensive integra-tion capabilities of the system’s server.

MDL supplies browsing applicationswith ISIS for easy, flexible access toMDL, customer, and third-party data-bases. Scientists, research management,and IT departments appreciate thecommon, consistent interface to bothcommercial and proprietary data.

Organizations can combine ISIS forExcel, Cheshire for ISIS, and SCULPT toprovide decision support and analysistools that work together for SARspreadsheets, physicochemical property prediction, Rgroup decomposition, and3D lead alignment. By automating the reporting and analysis, scientistscan speed lead identification and lead optimization.

Control Over SearchResults

An ISIS list is an electronicequivalent to a scientist’s list ofmaterials or journal references.ISIS lists can refer to reagents for

synthesis, products for screening orSAR, citations of reactions, chemicalsuppliers, activity results—any logicalcombination that will help scientistsfocus their analyses and make the right decisions.

ISIS’ sophisticated list managementallows sorting, collecting, analyzing, andreporting. These capabilities provide ahandle on corporate information as it is passed to desktop tools for easieranalysis and visualization.

Figure 3: Scientists value the easy-to-use, yet powerful list handling in ISIS. Combinations of text, numeric,and chemical structure searching can be saved to individual lists and then correlated with Booleanoperators to narrow or broaden search results.

Figure 2: The wide range of choices for analyzing data from ISIS include chemical spreadsheets, interactive charting visualizations, interactive molecular visualizations, the Web, ISIS/Base, or custom Visual Basic applications.

"We were looking for an

easy-to-use interface for

our discovery scientists that

would integrate chemical

structures from medicinal

and combinatorial chemistry

with biological data from

therapeutic areas and high-

throughput screening. Our

scientists were able to build

a browser that accesses

these multiple data sources

and pivots data from a single

user interface. The new

browser has proven its

effectiveness very quickly."

Dr. Edward W. PetrilloDirector of Combinatorial Drug Discovery Bristol-Myers Squibb

Developer Toolkits

The ISIS foundation includes a widevariety of application developmenttoolkits that are available on the serverand on the client in the environments supported by ISIS.

Whether your development goals areto centralize business logic on the serveror to provide sophisticated chemistrycomponents on the client (or both),ISIS provides the toolkits you need inyour environment of choice.

Server

ISIS/Direct—an object relationalimplementation of MDL chemicalsearch and indexing methods underOracle 8i

Chemscape Server—a Web interface to ISIS/Host

ISIS/Host API—a C interface to integration of data sources andstructure searching

ISIS/Host Command Line Interface—command line interface to ISIS

ISIS/Host Open Gateway—a program-mable data source interface to datasources not supported by MDL

ISIS/PL—a chemistry procedurallanguage called from ISIS/Host

Cheshire for ISIS—an object-orientedchemical structure automation environment

Client

ISIS/Object Library—a32-bit OLE automationserver for accessing ISIS from OLE supporting development tools

ISIS/ADK Pro—a collection of prepackaged OCX’s forcheminformatics applicationdevelopment

ISIS/PL—a chemistry procedural language called from ISIS/Base and ISIS/Draw

ISIS Add-In Manager—a frameworkfor packaged ISIS/PL routines

Cheshire for ISIS—an object-orientedchemical structure automation environment

Scalability AcrossUser Environments

ISIS operates at the scale you need,allowing scientists to work locally on aclient or on a network server at theclient level. Designed with connectionpooling, Oracle fetch constraints, andoptional buffering of query results, ISIScan efficiently handle very large usercommunities. Server-side ISIS/Host canbe installed on an individual machineand accessed by scientists across anorganization, or it can be distributedamong various departmental servers.

“Cheshire for ISIS

is based on a set of

abstract concepts including

‘collections’ and ‘mappings’

within an object-oriented

framework. The combination

of these concepts with the

rich dictionary of basic

operations allows Cheshire

to cover all the business

rules we need in the

process of structure

registration. The Cheshire

Studio will help us to

do the programming and

testing in a remarkably

efficient way.”

Dr. Upali BandaraBusiness Analyst, ZDW Scientific Information

BASF Aktiengesellschaft

MDL, Chemscape, Chemscape Server, Chime,Chime Pro, and SCULPT are registered trademarksand Cheshire, ISIS, ISIS/ADK Pro, ISIS/Direct,and ISIS/Object Library are trademarks of MDLInformation Systems, Inc. Microsoft is a registeredtrademark of the Microsoft Corporation. Oracle is aregistered trademark and Oracle 8i is a trademarkof the OracleCorporation. Spotfire is a registeredtrademark of Spotfire, Inc. All other productnames may be trademarks or registered trademarksof their respectiveholders.©Copyright 2000 by MDL Information Systems, Inc.All rights reserved. ISIS/01-00/7.5K

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Information Systems, Inc.

Popular DiscoveryPlatforms

ISIS products run on the desktopclient or on the server which hosts thesystem’s integration capabilities. Thefoundation technology supports a widerange of platform configurations forboth operating system support anddevelopment.

ISIS Technology on the Server

ISIS/Host, Cheshire for ISISSun SolarisSGI IRIXIBM RS/6000 AIXMicrosoft Windows NT ServerCompaq Open/VMS Alpha

Chemscape ServerNetscape Enterprise Server (Sun, SGI, AIX, NT)Microsoft Internet Information Server (NT only)

ISIS Technology on the Client

ISIS/Base and ISIS/DrawMicrosoft Windows 95, 98, and NTMacintosh

Chime and Chime Pro for Web BrowsersMicrosoft Windows 95, 98, and NTMacintosh

ISIS for Microsoft ExcelMicrosoft Windows 95, 98, and NTMacintosh

ISIS Gateways and DevelopmentToolkits on the Server

Supported ISIS/Host GatewaysMDL Molecule DatabaseMDL Reaction DatabaseORACLE RDBMSMDL Relational Chemical GatewayBeilstein Crossfire Server Database

Gateway

About MDL

MDL Information Systems (“MDL”)is the recognized leader in discoveryinformatics for the life science andchemical industries. MDL software,content, and services provide the enterprise framework for identifyingsuccessful new products. MDL is aninternational business headquartered in San Leandro, CA with offices world-wide. MDL Information Systems, Inc. is a wholly owned subsidiary of ElsevierScience, Inc.

“After evaluating

the options, we

determined that MDL

tools and technology

will help us build the

robust informatics

infrastructure that

we need to support

the cutting-edge

applications we plan for

the future. We have

aggressive goals for

R&D productivity and

our relationship

with MDL will help

us to provide our

scientists with the

tools to achieve them.”

Martyn WilkinsDirector, Research Information Systems

AstraZeneca Pharmaceuticals

ISIS