Recent developments in de novo design and scaffold hopping

Curr Opin Drug Discov Devel. 2008 May;11(3):365-74.


This review covers the developments in the fields of de novo ligand design and scaffold hopping since 2006. De novo ligand design was introduced in 1991 as a purely structure-based method to suggest ligands for synthesis and was later augmented by ligand-based approaches. Both structure-based and ligand-based methods identify pharmacophores, as well as shape constraints, and subsequently match these with complementary features embedded into small-molecule topologies. Recently, significant attention has been paid to de novo ligand design in combination with biophysical fragment screening and X-ray structure elucidation. Scaffold hopping has evolved from a niche application of de novo design into a rapidly expanding suite of different software tools, which are used extensively in the pharmaceutical industry.

Publication types

  • Review

MeSH terms

  • Animals
  • Computer Graphics
  • Computer Simulation
  • Computer-Aided Design*
  • Drug Design*
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Protein Conformation
  • Small Molecule Libraries
  • Structure-Activity Relationship
  • Technology, Pharmaceutical / methods*


  • Ligands
  • Small Molecule Libraries