Compound optimization in drug design

SwissBioIsostere is a knowledgebase that provides information on more than 4.5 million molecular substructural replacements extracted from literature and that are useful for compound optimization in drug design. It provides a tool for replacements for a single substructure (e.g. an amide group) or a particular substructure of interest (e.g. carboxylic acid vs tetrazole).


  • Chose the right replacement for a structure known to lead to side-effects while keeping the desired activity of the compound
  • Get bioactivity information about a particular replacement

Key features

  • Very rapid query (1 sec to 1 min) based on a modified version of the Hussain and Rea algorithm (JCIM 2010)
  • High-confidence results mined from the ChEMBL database that has been filtered to keep only clearly annotated information
  • Extensive list of all published replacements for each substructure of interest (up to three attachment points)
  • Clear results presentation with possibility to filter and aggregate the data on different levels
  • Easy data exportation via a copy to the clipboard or download of a csv-file
  • Provided additional information: observed frequency, activity difference distribution, success-based score, and chemical similarity between the fragments.


Wirth, M., Zoete, V., Michielin, O., and Sauer, W.: SwissBioisostere: a database of molecular replacements for ligand design, Nucleic Acids Research (2013) 41 (D1), D1137-D1143. (PDF)


SwissBioisostere is developed and copyrighted by SIB Swiss Institute of Bioinformatics and its exclusive commercial representative GeneBio.
Access is free for non-commercial use. Access by commercial entities is subject to the licensing conditions outlined in the GeneBio License Agreement (PDF).

Please contact us for further details.

SwissBioisostere website