Chemaxon Tools Julian Fowler Chemaxon UGM - September 26 th , 2012 - - PowerPoint PPT Presentation

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Chemaxon Tools Julian Fowler Chemaxon UGM - September 26 th , 2012 - - PowerPoint PPT Presentation

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Sharing Chemical Data with Collaborators using Chemaxon Tools Julian Fowler Chemaxon UGM - September 26 th , 2012 Example Collaboration Constellation Pharmaceuticals and Genentech Enter Broad Epigenetics Drug Discovery Collaboration CAMBRIDGE,

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Sharing Chemical Data with Collaborators using Chemaxon Tools

Julian Fowler Chemaxon UGM - September 26th, 2012

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Example Collaboration

Constellation Pharmaceuticals and Genentech Enter Broad Epigenetics Drug Discovery Collaboration

CAMBRIDGE, Mass. – January 17, 2012 – Constellation Pharmaceuticals, Inc., today announced that it has entered into a major strategic agreement with Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), to launch a broad collaboration based on the science of epigenetics and chromatin biology to discover and develop innovative treatments for cancer and other serious diseases.

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Collaboration: Registration’s Role

Submission Structure Checker Standardizer Staging Triage Registration

Standard Representation Reliably Determine Uniqueness Clean Structures Robust Searching

Chemical Registration Workflow Chemical Database

  • How can we enable Constellation to meet the

requirements for registering new compounds?

  • How can we effectively share data?
  • Acknowledge a problem with existing registration system
  • How quickly can we implement a solution?

Challenge: Working as part of a collaboration

Structure Validation Rules

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Expectations

Compound Data

  • Registered correctly
  • Clean structures

CRO’s

  • Reorder/Remake

compound

  • Inactive batch?

Physical Samples

  • Constant flow of

samples

  • Shipping samples

Analysis Results

  • Timely transfer of data
  • High confidence level
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  • Start-Up Stage
  • Manageable number of

MedChem compounds

  • Small established screening

library

  • Registration a non-issue

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Compound Management

50 000 100 000 150 000 200 000 250 000 300 000 350 000 400 000 450 000 2008 2009 2010 2011 2012 Numbe of Compounds Year

Unique Compounds Added vs. Year

Compounds Registered Total Library Size 2009/09 2009/11 2010/01 2010/03 2010/05 2010/07 2010/09 2010/11 2011/01 2011/03 2011/05 2011/07 2011/09 2011/11 2012/01 2012/03 2012/05 2012/07 2012/09 Number of Unique Compounds

MedChem Compounds By Month

  • Maturing Stage
  • MedChem scale up
  • CRO scale up
  • Small/midsize library addition
  • Registration impacts drug

discovery process

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  • Compound submission, triage and registration completed in
  • ne day
  • Aggressive schedule leaves little room for error
  • Get registration wrong then assay analysis and reporting

could be affected

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Get registration right first time

MedChem Lead Discovery

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Problem: Challenging Stereochemistry

CPI-585.01 CPI-585.02 X09345.01 X09345.02 CPI-585.03 X10945.01 CPI-585.04 X18345.01 Constellation New Batch Collaborator New ID

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Problem: Synchronize Registration

Constellation Database Collaborator Database

Registration CPI-1198745 X15667294

Results

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How are we solving these problems?

  • New registration system
  • Robust and reliable
  • Clean structures
  • Fast efficient searching

Chemical Database

  • Handle stereochemistry consistently
  • Registrar plays a significant role
  • Registrar knows the chemical space
  • Provide tools to determine uniqueness

Stereochemistry

  • Implement the same registration rules as our

collaborator

  • Rules are complex

Synchronize Registration

How can we incorporate these rules and create a system in less than 6 months?

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Chemaxon Tools

Standardizer Structure Checker

  • Clean structures
  • Detect and fix issues
  • Customized checks
  • Integrated in batch
  • Canonical structure representation
  • Consistent standardization
  • Fully customized
  • Integrated in batch

JChem Cartridge

  • Chemical intelligence
  • Robust search capability
  • Oracle based
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How does Structure Checker help us?

Wedge Bonds Remove explicit Hydrogen atoms

<WedgeErrorChecker fixMode=“fix” fixerClassName="chemaxon.fixers.WedgeCleanFixer"/> <ExplicitHydrogenChecker charged="true" fixMode="fix" fixerClassName="chemaxon.fixers.ExplicitHydrogenFixer" isotopic="false" lonely="true" mapped="true" radical="true" wedged="true"/>

Images from Chemaxon User Documentation

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How does Standardizer help us? Mesomers

Transformation Transformation

Images from Chemaxon User Documentation

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How does Standardizer help us? Tautomers

Transformation Transformation

Images from Chemaxon User Documentation

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Implementing Registration Rules

Standardizer svc = new Standardizer(new File(“constellation_rules.xml")); svc.standardize(mol);

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Chemical Registration System

  • Transform chemical structures into a

customized, canonical representation

  • Ensure CRO provides compound data in a

consistent format

  • Share compound data with our collaboration

colleagues in a consistent format

Challenge: Build a robust and reliable chemical database

  • JChem Cartridge
  • Structure Checker
  • Standardizer

Strategy: Select the right technologies

  • Simple and easy to use
  • Registrar role in determining uniqueness
  • Register single/bulk compounds
  • Robust search capabilities
  • Easier to correct structures after registration

Features : System attributes

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Successfully sharing chemical data with collaborators

  • For a small biotech company sharing chemical data within a

collaboration setting can be especially challenging

  • Making Structure Checker and Standardizer part of our chemical

registration workflow has been a smart move

  • These tools have allowed us to rapidly develop a new

registration system and also address the more important issue of reliably sharing data with our collaborators

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Team Structure

Resource Primary Role Bill Amsbaugh Director Systems architecture design, component design, program management Ashan Tissera Senior Software Engineer Architecture implementation, web applications, database design, lead offshore team Julian Fowler Lead Engineer Automation applications, web applications, Bioinformatics algorithm development, lead offshore team Joe Marchionna Principle Engineer Robotic integration, mechanical engineering, software design, application development R-Systems (Delhi) Infrastructure development Jubilant (Bangalore) Scientific application development DBA Zone (Pittsburgh) Database Administration

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Acknowledgements

Medicinal Chemistry

Brian Albrecht Mike Hewitt Alex Taylor Victor Gehling Alex Cote Rishi Vaswani Yves Leblanc Alex Gagnon

R&D/ Management

JC Harmange Mike Cooper Jim Audia

Automation Bill Amsbaugh Julian Fowler Ashan Tissera Joe Marchionna Chemaxon

Doug Drake Jon Patterson David Deng

Jubilant

Asath Fernando Senthil Kumar

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