Glossary

Explanation of terms used by DrugBank

Lipinski's rule of five

Synonyms:
Lipinski's rule, Lipinski's rule of 5, Rule of 5, Rule of five

Lipinski's rule of five is a rule of thumb that describes the drugability of a determinate molecule. This rule helps to determine if a biologically active chemical is likely to have the chemical and physical properties to be orally bioavailable. The Lipinski rule bases pharmacokinetic drug properties such as absorption, distribution, metabolism and excretion on specific molecular properties such as:

  • No more than 5 hydrogen bond donors
  • No more than 10 hydrogen bond acceptors 
  • Molecular mass less than 500 Da
  • Partition coefficient not greater than 5

The violation of 2 or more of these conditions predicts a molecule as a non-orally available drug.

The name of "rule of five" comes from the fact that all the conditions have multiples of 5 as the determinant conditions.1,2

In DrugBank, the result of the analysis based on the Lipinski's rule of five is studied using the prediction software ChemAxon and the value found in the predicted properties table will be presented as "Yes" or "No" depending if the molecule follows or no at least 3 conditions of the rule of five.

References:

  1. Benet LZ, Hosey CM, Ursu O, Oprea TI: BDDCS, the Rule of 5 and drugability. Adv Drug Deliv Rev. 2016 Jun 1;101:89-98. doi: 10.1016/j.addr.2016.05.007. Epub 2016 May 13. [PubMed:27182629]
  2. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26. [PubMed:11259830]