Oncology exploration: charting cancer medicinal chemistry space. Academic Article Review uri icon

start page

  • 149

end page

  • 159


  • Approaches for the experimental determination of protein-ligand molecular interactions are reliant on the quality of the compounds being tested. The application of large, randomly designed combinatorial libraries has given way to the creation of more-focused 'drug-like' libraries. Prior to synthesis, we wish to screen the potential compounds to remove undesired chemical moieties and to be within a required range of physiochemical properties. We have used a principal-component analysis (PCA) computational approach to analyze the 3D descriptor space of active and non-active (hit-like) cancer medicinal chemistry compounds. We define hit-like those molecules passing the unmodified OpenEye FILTER program. Our analysis indicates that these compounds occupy quite different regions in space. Cancer-active compounds exist in a much greater volume of space than generic hit-like space and most of them fail the commonly applied filters for orally bioavailable drugs. This is of great significance when designing orally bioavailable cancer target drugs.

date/time value

  • 2006

Digital Object Identifier (DOI)

  • 10.1016/S1359-6446(05)03688-3

PubMed Identifier

  • 16533713


  • 11


  • 3-4


  • Antineoplastic Agents
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Principal Component Analysis