Integrating JChem and Marvin into the Integrity ® Drug Discovery and Development Portal Rosa Alentorn, Gerard Chiva and 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 Stereochemistry, salts – Standardizer tool

Before v Peptides v

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

- >[O:1]=[C:2][#6:3]" /> >[C:1][O:2]" /> >[N]" /> >[N:2][C:1]" /> >[O:1]=[N:2][#6:3]" /> >[I:1]" /> >[F:1]" /> >[C:1]" /> >[In:1]" /> >[Tc:1]" /> 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