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Real World Chemistry

Virtual discovery for the real world

Joe Mernagh19 May 2005

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Introduction – Joe Mernagh

15 Years Cap Gemini• Consultant: knowledge systems, IT strategy, Life Sciences R&D

• Senior Manager Life Sciences Global Management Unit

4 years Evotec OAI• Chief Knowledge Officer

• Executive manager responsible for Knowledge Management and IT

• Innovative drug discovery solutions

Active Dynamics• Independent consultant and interim manager

• Focus on companies involved in drug discovery

• Projects with potential for long term value creation

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Why get excited about virtual discovery ?

Virtual discovery, both rational and high throughput, is playing an ever greater role in the discovery process

Virtual discovery

• Cheap

• Immediate, rapid experiments

• No shelf-life or repeatability issues

• No physical infrastructure

• Coverage of all accessible chemistry

space

Laboratory based discovery

• Expensive

• Long setup stage, slow experiments

• Compounds and assays degrade

• Laboratory infrastructure

• Chemistry space is defined by access

to physical compounds

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How does virtual discovery help solve the R&D bottleneck ?

Only virtual techniques, discovering highly profiled candidate molecules for laboratory testing, can address the bottleneck

• Genomics and proteomics research has given the world a wealth of potential druggable targets to work on and has started a race to identify appropriate small molecules

• High throughput laboratory chemistry and screening technologies have not been powerful enough to deal with the avalanche of targets

• There is no appetite to scale up physical chemistry and screening beyond current technology limitations

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Introducing on-demand in-silico discovery

In virtual discovery, the only constraints are the quality of the algorithms and the availability of processing power

• The complexity of virtual discovery technology is a major constraint for SMEs - there is an opportunity to provide a complete ASP service for discovery informatics

• Processing requirements for virtual discovery are potentially very large and very irregular – an on-demand facility combining leading edge software and large scale computing power might be highly attractive proposition for companies of all sizes

• The combination of unique virtual discovery technology and massive computing power will create wholly new ways of exploring chemical space

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So, what is the big idea ?

The idea is to allow researchers to buy virtual drug discovery capability on an as-needed basis by plugging their workstations

into the internet

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The Real World Chemistry in-silico discovery centre

Large Scale Computing Facility

ChemAxon Discovery Tools

Java GUI

Virtual Synthesis Engine ChemAxon Reaction Library

Virtual Compound Space

Web Services Access

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What services might this provide ?

SynthesiseNew VirtualCompounds

FindChemical

Route

IdentifyDrug-like

Candidates

ProfileCompounds

DesignAnalogs

Design De-novoCompounds

ScreenCompounds

Diversity andCluster Analysis

Find compounds and scaffolds to fit a specific bioavailability and physico-chemical profile

What is the pKa, LogD, LogP, polar surface area etc of my compounds ?

Input compound - create new, synthetically feasible analogs

Fragment based rational design of de-novo compounds

Give me a synthetic route and reagents for my selected compounds

Create me a new virtual library from my selected reactions and inputs

Screen selected compounds for efficacy, ADME and toxicity

How chemically diverse are my selected compounds ?

Large Scale Computing Facility

ChemAxon Discovery Tools

Java GUI

Virtual Synthesis Engine

ChemAxon Reaction Library

Virtual Compound Space

Web Services Access

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Why ChemAxon technology is ideal for building an on-demand in-silico discovery platform

Chemical terms = Smart Reactions =synthetically feasible products

Profile compounds:elemental analysis, pKa, LogP, LogD, polar surface area, charge distribution, refractivity, major microspecies etc

Library of key preparative reactions

Powerful java based structure, reaction and query editor

Chemical and pharmacophore similarity searching

High performance fingerprint and graph based topology searching

Optimised high throughput virtual screening

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You can contribute to making this a reality

At this User Group Meeting, you can participate :

• Discussion about the composition and value of an on-demand virtual discovery centre

• Survey of market interest in such a facility

… or back of envelope design over a beer !

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You can contribute to making this a reality

• Help us develop the GUI environment which will provide the entry point to the virtual discovery tools

• Hook in your virtual screening technology (target based virtual screening, ADME/T models etc)

• Be an early adopter and get an opportunity to contribute your particular requirements during the design process

As a partner, you can participate in an exciting new business proposition which already has the interest of a leading global provider of information technology services :

There is a real commercial opportunity to be part of a unique, ground-breaking project