Solutions for Cheminformatics

April 2010

Company and product overview

ChemAxon fingerprint

• Founded in 1998, based in Budapest, Hungary

• Database management tools, drug design and discovery

• Pharma, biotech, academia

• Representation in Europe, US, Japan, India and China

• Wide industry reach >300 corporate clients

Product Map

Active across the Globe

Active across the Globals

The ChemAxon Advantage

• Comprehensive– Visualisation /drawing, data

management, drug discovery – From toolkit to fullkit

• Compatible– Mutliple platform support on all

products– Customizable to own needs– API – Java, .NET, SOAP– Common core across all products

• Interface– Intuititive “as you like it” GUI– Easy to adopt/adapt

• Performance– Scalability– Speed

• Quality– Best in class products– Customer developed and tested

• Support– Rapid response (within 24 hr)– Project and integration

management

• Experience– 11 years cheminformaniacs– Development projects with biotech,

chem services and publishers– Dozen successful migration

projects

GSK Case Study

• Adoption of full ChemAxon toolkit July 09.

• Replacing Daylight and ISIS globally

• Implementing Cartridge, IJC and JC4XL

• 3 months evaluation, 3 months pilot projects.

• Implementation ongoing – takes 12 months

• Choses ChemAxon for:– Performance– Ease of integration/implementation– Flexible license model, includes partners– Price (cost effectiveness)

35 Integrator Partners

• Analysis and reporting

• Biological Data Management

• ELN

• Scientific Publishing

• Data Mining

• Workflow/pipeline tools

• Online Education

• SAR

• Laboratory Information Management

• Analytical chemistry

• Chemical inventory

• Chemical registration

• Sample management

• Patent search

• Toxicity and metabolites prediction

Applications integrating ChemAxon

 Target

IdentificationHit

GenerationLead

GenerationLead

Optimization

Knowledge database and management  

ELN  

Scientific Publishing  

Data Mining/ Analysis/ Visulisation  

Workflow/pipeline tools  

LIMS        

Chemical inventory      

Chemical registration      

Sample management      

SAR analysis    

Toxicity and metabolites prediction, ADMET        

The Marvin family

MarvinSketch MarvinView MarvinSpaceAvailable as applets for HTML pages and components for standalone apps (full API)

Structure, query & reaction editing

Individual and structure table visualization

Macromolecule visualization

MarvinSketch/View http://www.chemaxon.com/MarvinSketch_View.ppt

MarvinSpace http://www.chemaxon.com/MarvinSpace.ppt

Marvin Development History1998

Applets, Molfiles, stereo support, Windows, Unix

SMILES, SMARTS, PDB, Rgroups, isotopes, shortcuts, Marvin Beans

Ball and stickJPG, PNG, SVG, Cut&Paste with Isis/ChemDraw, 2D cleaning, (de)aromatization, reaction drawing

20001999

SDF, RDF, XYZ animations, CML, templates, compressed formats, Swing, 3D models

2001

Mac support, signed applets, Java Web Start, atom mapping

Partial charge,

pKa, logP/logD,

3D optimization, radicals,abbreviated groups

Marvin file format, enhanced stereo, shapes, text boxes, multiple groups, link nodes, TPSA, recursive SMARTS, Donor/Acceptor, electron arrows,

2004

2003

2005

Tautomers, resonance, lone pairs, conformers, 3D sketching, MarvinSpace,

Topology analysis, presentation quality graphics,...

2006

More Plugins,more R-groups,EMF, PDF and Mol2,Improved property storage in MRV, SDfiles and Rdfiles..NET support in MarvinBeans.

2002

2007

Structure to name, Coordination compounds, Polymer drawing, OLE, Markush enumeration pluginConfigurations

2008

Name to structure, OLE 2, Chemical Terms,Customizable GUI

2009

Transparent images.NETApplet loading speed upSprout drawing

Calculator Plugins

Calculator Plugins http://www.chemaxon.com/Calculator_Plugins.ppt

Elemental AnalysisStructure to NameProtonation pKa, Major Microspecies, Isoelectric PointPartitioning logP, logD

Charge Charge, Polarizability, Orbital Electronegativity

IsomersTautomerization,Resonance, Stereoisomer

ConformationConformer, Molecular Dynamics, 3D Alignment

GeometryTopology Analysis, Geometry, Polar Surface Area (2D), Molecular Surface Area (3D)

Markush enumerationOther

Hydrogen Bond Donor-Acceptor, Huckel Analysis,

Refractivity, Structure Frameworks

Structure based calculations are available from the Marvin and Instant JChem GUI, cxcalc command line tool and the API/ Available as functions of Chemical Terms expressions.

Chemical Naming

Structure to Name/ Name to structure

Supported nomenclatures :

• Chains, Monocycles/ Traditional names with and without heteroatom/ Spiro ring systems/ Ethers/ Common characteristic groups, Ionic compounds/ Unlimited number of atoms and rings/ All atom types /Stereochemistry/ etc.

Usage:

• drag&drop or copy&paste to MarvinSketch

• Label updated in real-time

• Automatic format recognition

• Batch from command line

• Name to structure conversion of documents

• www.chemicalize.org

Chemicalize the Web: http://www.chemicalize.org/

JChem family

JChem Base JChem Cartridge Instant JChem JChem for Excel

API for structure searching and database handling

Tight Oracle SQL integration

Desktop application for scientist

Marvin and JChem functionality

Available from Java, .NET and Web services

SQL functions for chemistry

Access local and remote databases

Excel functions, sorting, filtering, charge etc…

JChem development history2000

Oracle, MySQL, SQLServer, Access, hashed fingerprints, substructure and similarity search

DB2, PostgreSQL, Rgroup searching

Reaction searching, fragmentation, reaction processing, standardization, pharmacophores, screening

20022001

Clustering, diversity

2003

R-decomposition,R-enumeration, reaction library, custom fingerprints, random synthesis, link nodes…

2005 2006

Tautomer search, Instant JChem reaction similarity, Library MCS, GUI for Standardizer/ Reactor …

2007

Calculated columns, Installer,Tautomer Duplicate filtering, Query tables, Markush tables, Speed

enhancements for

JChem Cartridge,form design, relational data for Instant JChem ...

Cartridge, enhanced stereo searching, recursive SMARTS, Chemical Terms, virtual synthesis

2004

2008

Position variation queries, Instant JChem:-- Federated search, -- Cartridge support...

2009

JChem for ExcelJChem Web Services, AJAX Polymer search Data Sgroup search Faster SSS Metabolizer

Features

• Fast and sophisticated searching(chemical and non-chemical data, Chemical Terms filter, many options)

• Custom standardization

• Calculated columns

• Combinatorial Markush structure tables

Interfaces

• Integration with most relational database engines

• JChem Cartridge for tight Oracle SQL integration

• JSP and AJAX open source web examples

• Desktop-ready through Instant JChem

• JChem Web Services available

JChem Base

DB2

Structural Search http://www.chemaxon.com/Structural_Search.ppt

JChem Base http://www.chemaxon.com/JChem_Base.ppt

Searching in combinatorial Markush structures

Combinatorial Markush structure registration and search

• Markush features handled in search & enumeration:

― R-groups (nesting to any depth)

― Atom lists, bond lists

― Position variation bond

― Link nodes and repeating units

― Homology groups

• Compatible Markush enumeration plugin

• Not all query features supported

Detailed description:

http://www.chemaxon.com/product/markush_search.html

JChem Cartridge for Oracle

• Access JChem functionality via SQL functions

• All search features of JChem Base

• JChem index for chemical data in arbitrary database structure

• Chemical filters and property predictors using Chemical

Terms

• Standardization (structure canonicalization) during registration

• Structure format conversions

• 2D, 3D image generation

• Library enumeration using

virtual reactions and

Markush structures

JChem Cartridge http://www.chemaxon.com/JChem_Cartridge.ppt

Instant JChem

Desktop application for local and remote chemical database management, search and structure based prediction

• Simply connect to external databases and share your native database simultaneously

• Powerful search functionalities

• Scalable – explore large datasets (106 +)

• Dynamically predict properties using Calculator Plugins

• Apply canonicalization rules for import and viewing

• Wide import / export options

• Merge data sets into a single set

Instant JChem: http://www.chemaxon.com/conf/Instant_JChem.ppt

JChem for Excel

• Microsoft Excel integrated solution for Marvin and JChem functionality

• Use Excel’s powerful features: Functions, Sorting, Filtering, Charts…

• Implemented in C# .NET, and Visual Studio

– Proof that ChemAxon APIs can be used in a Java-less .NET environment

• Easy to install and deploy

JChem Web Services Server

• Web Services integration of JChem functionality

― JChem Search

― Molecular Conversion

― Standardizer

― Chemical Terms

• Enables SOAP capable (e.g. AJAX, Perl, Python) programming environments

• Standalone server

― Chainable with other web services

• Easy to install and deploy

Canonicalization with Standardizer

Standardizer http://www.chemaxon.com/Standardizer.ppt

• Structure canonicalization– Mesomers– Tautomers– Solvent and counter ion removal– Aromatization, dearomatization– Explicit/implicit hydrogen conversion– Stoichiometry expansion– Stereo manipulations– 2D cleaning– Template based cleaning

• Custom rules

• Structure checker

• Availability– JChemBase– API– Batch processing

Drug discovery toolsJKlustor ScreenProfiling, analysis, diversity Virtual screening by topological

descriptors

Fragmenter ReactorLibrary profiling and reactant generation

Virtual reactions and synthesis

Virtual Screening with Screen

Screen http://www.chemaxon.com/Screen.ppt

• Active set dependent automated optimization

• Wide range of descriptors– native chemical fingerprint– pharmacophore fingerprint

• customizable definitions• functional group based mapping• calculation based mapping

– calculator plugins– user defined descriptors– combined descriptors

• Tanimoto and Euclidean metrics– Tunable parameters

• normalization• weighting• scaling• directing (asymmetric)

Clustering with JKlustor

JKlustor http://www.chemaxon.com/JKlustor.ppt

Clustering performance comparison

0102030405060708090

0 20000 40000 60000 80000 100000 120000

Input structure count

Ru

nn

ing

tim

e (m

in) LibraryMCS

Jarvis-PatrickWard-Murtagh

• Similarity and structure based, Hierarchical and non-hierarchical methods– hierarchical

• Ward• MCS

– non-hierarchical• Jarvis-Patrick

• Wide range of descriptors– Chemical fingerprint– Pharmacophore fingerprint– Calculator plugins– User defined custom descriptors

Library profiling with Fragmenter

Fragmenter http://www.chemaxon.com/Fragmenter.ppt

• Transformation based fragmentation method

– Customizable transformations– RECAP transform set– Synthetically relevant transformations– Labeled connections– Options to keep fragment feasible

(no ring opening, limit fragment size, limit the number of connection points, etc)

– Fragment statistics– Activity based scoring

• High throughput fragmentation• Simple rule cleaving carbon-carbon single bond next to a hetero

atom (CCQ)

• Functional groups remain intact

• Very fast algorithm (no ring perception, no substructuresearch)

• R-group decomposition

Virtual Synthesis with Reactor • Reaction Engine

– Converts reactants according to a given reaction scheme– Chemo-, regio- and stereospecific reactions are supported by

the integrated property calculation functions (if the reaction contains rules in Chemical Terms format).

– Compatible with the popular molecule, reaction file and reaction mapping formats.

• Reactor Application– An application of the

reaction engine for combinatorial chemistry.

– Wizard-like applicationand reaction editor.

– Built in testing system.

Metabolizer

Virtual reaction based metabolite enumeration tool

xenobiotic metabolic pathways prediction

metabolic stability

metabolically sensitive groups and major metabolites

can be customized by various biotransformation libraries

Human phase I, xenobiotic CYP450 biotransfomation library UNDER DEVELOPMENT

Under Development

• Integration of Screen descriptors and metrics into Cartridge

• Structure Checker for Standardizer

• New features for Instant JChem, like multi tier architecture, improved reporting capabilities, improved visualisation

• Improve Markush structure handling in JChem Base / Cartridge / Marvin

• Metabolite and metabolic stability prediction

• Human CP450 biotransformation library

• Multistep reactions in Marvin and JChem

• Compound registration system

• 3D similarity searching based on flexible alignment

• SKC support

Visit other technical presentations

MarvinSketch/View http://www.chemaxon.com/MarvinSketch_View.ppt

MarvinSpace http://www.chemaxon.com/MarvinSpace.ppt

Calculator Plugins http://www.chemaxon.com/Calculator_Plugins.ppt

Chemical Naming http://www.chemaxon.com/conf/Naming.ppt

Structural Search http://www.chemaxon.com/Structural_Search.ppt

JChem Base http://www.chemaxon.com/JChem_Base.ppt

Markush Search http://www.chemaxon.com/conf/Markush_development.ppt

Instant JChem http://www.chemaxon.com/conf/Instant_JChem.ppt

JChem for Excel http://www.chemaxon.com/product/jc4xl.html

JChem Cartridge http://www.chemaxon.com/JChem_Cartridge.ppt

Standardizer http://www.chemaxon.com/Standardizer.ppt

Screen http://www.chemaxon.com/Screen.ppt

JKlustor http://www.chemaxon.com/JKlustor.ppt

Fragmenter http://www.chemaxon.com/Fragmenter.ppt

Reactor http://www.chemaxon.com/Reactor.ppt

Find out more

• Product descriptions & linkswww.chemaxon.com/products.html

• Forumwww.chemaxon.com/forum

• Presentations and posterswww.chemaxon.com/conf

• Downloadwww.jchem.com/licensefrset.html