Integrating JChem and Marvin into the Integrity® Drug

Discovery and Development Portal

Rosa Alentorn, Gerard Chivaand Ann Wescott

ChemAxon UGM, 7-8 June 2006

Why ChemAxon?

• Modern technology• Java-based• Ease of technical integration• Ease of use of tools by end users –

both internal and clients• ChemAxon's responsiveness

Challenges encountered

• Technical• Chemistry• Workflow

Challenges encountered

Technical• Minimal problems were found by

our technical staff as they worked to implement JChem and Marvin both in-house and in our products

Challenges encountered

Chemistry• Peptides• "Any" search using Marvin applet• Stereochemistry• Salts

• Tautomers

Challenges encountered

Workflow• Searches retrieved "too many"

compounds, requiring manual review and excessive time investment

Solutions

• Technical• Chemistry• Workflow

Solutions

Technical• Technical issues were resolved via

contact with ChemAxon staff

Solutions

Chemistry / Workflow• Peptides, "any" search – v. 3.1.5• Stereochemistry, salts –

Standardizer tool

Before v. 3.1.5

Peptides

v. 3.1.5

Without Standardizer

Search for isomers, ionic salts and solvates of ketoprofen

Without Standardizer

Searching by substructure retrieves 70 structures, many of which are "not desired," for example:

Standardizer

Designed to recognize the same compound represented with different chemical forms

In Prous Science databases, also used to recognize salts, solvates, isomers, tautomers, etc., of the same compound with a single search

Carboxylates

ClearStereo

Fragment removal

Ex: Ketoprofen derivatives

- <StandardizerConfiguration Version="0.1">

- <Actions>

  <Removal ID="removal" Method="keepLargest" Measure="atomCount" />

  <ClearStereo ID="clearstereo" />

  <Aromatize ID="aromatize" Type="general" />

  <ImplH ID="implh" Lonely="true" Isotope="true" Charged="true" Radical="true" Mapped="true" Wedged="true" />

  <Transformation ID="enol" Structure="[#8:1][C:2]=[C:3]>>[O:1]=[C:2][#6:3]" />

  <Transformation ID="olato" Structure="[C:1][O-:2]>>[C:1][O:2]" />

  <Transformation ID="ammonium" Structure="[N-]>>[N]" />

  <Transformation ID="ammonium2" Structure="[H:3][N+:2][C:1]>>[N:2][C:1]" />

  <Transformation ID="nitroso" Structure="[#8:1][N:2]=[C:3]>>[O:1]=[N:2][#6:3]" />

  <Transformation ID="123I" Structure="[123I:1]>>[I:1]" />

  <Transformation ID="131I" Structure="[131I:1]>>[I:1]" />

  <Transformation ID="125I" Structure="[125I:1]>>[I:1]" />

  <Transformation ID="18F" Structure="[18F:1]>>[F:1]" />

  <Transformation ID="11C" Structure="[11C:1]>>[C:1]" />

  <Transformation ID="111In" Structure="[111In:1]>>[In:1]" />

  <Transformation ID="99Tc" Structure="[99Tc:1]>>[Tc:1]" />

  </Actions>

  </StandardizerConfiguration>

Standardizer configuration

Chemical structures are stored "as drawn" and in standardized form

Users can choose to search using the standardized structure or not

Search results display the chemical structure "as drawn"

Using "Standardized" structure

With Standardizer

Search for isomers, ionic salts and solvates of ketoprofen

10 structures retrieved, all “desired,” for example (1-6):

10 structures retrieved, all “desired,” for example (7-10):

Wish List

• Greater ease in version upgrades• JChem Manager with enhanced user

friendliness• Ability to display long lists of

structures• Tautomers• Markush storage + retrieval

capabilities

Next Steps

• Investigate how to use Standardizer to transform tautomers

• Implement Standardizer in end-user products

• Continue open communication with ChemAxon