Lipinski’s rule-of-five

Lipinski’s rule of five (RO5) is used to evaluate druglikeness of a chemical compound possessing properties that would make it a likely or potential drug in humans (Lipinski et al., 2001). The oral activity of a drug compound is predicted by calculating certain molecular parameters like log P (partition coefficient), polar surface area, number of hydrogen bond donors, number of hydrogen bond acceptors and molecular weight. The rule states that most drug candidates with good membrane permeability must have log P ≤ 5, number of hydrogen bond acceptors ≤10, and number of hydrogen bond donors ≤5. In general, an orally active drug has no more than one violation of the given criteria.

Lipinski’s rule of five is helpful in describing molecular properties of drug compounds required for estimation of important pharmacokinetic parameters such as absorption, distribution, metabolism and excretion. The rule is helpful in drug design and development (Lipinski et al., 2001; Ertl, Rohde & Selzer, 2000; Veber et al., 2002).