Core Properties

A number of core properties are available to help guide your compound design:

  • Molecular Weight
  • Number of rotatable bonds
  • Flexibility
  • Number of hydrogen bond donors
  • Number of hydrogen bond acceptors
  • Topological polar surface area.

Why are these properties important?

Many simple compound characteristics or physicochemical properties have been used to define ‘drug-like’ compounds.  Numerous rules have been developed based on these properties, the best known being Lipinski’s ‘Rule of Five’ (Lipinski et al. Adv. Drug Deliv. Rev. (1997) 23 pp. 3-25). A review of many of these rules can be found in (Garcia-Sosa et al. Curr. Med. Chem. (2012) 19 pp. 1646-1662). These rules can provide useful guidelines that help to avoid venturing into high risk property space, e.g. large, lipophilic compounds.

However, while some of these rules may provide useful guidelines, they should be applied with a number of important caveats in mind:

  • Hard cut-offs or filters draw artificially harsh distinctions between similar compounds and can lead to missed opportunities
  • The rules usually relate to a specific project objective and may not apply to your specific project objective
  • Metrics based on similarity with successful drugs do not take into account the property differences with the background of unsuccessful compounds
  • Inclusion of multiple, correlated properties can lead to over-counting of the same risk factor