In their much quoted paper of 1997, Lipinksi et al. studied a large set of known drugs and found that the majority obeyed a set of rules ( called "the rule of 5" from the cutoff values for each of the four parameters that define the "drug-likeness" of the potential drug candidates: all of these values are close to five or a multiple of five). The original publication (Christopher A. Lipinski, Franco Lombardo, Beryl W. Dominy, Paul J. Feeney "Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings", Adv. Drug Delivery Rev., 1997, 23(1-3), 3-25) states that:

The "rule of 5" states that: poor absorption or permeation is more likely when:

1. There are more than 5 H-bond donors (expressed as the sum of OHs and NHs);

2. The MWT is over 500;

3. The LogP is over 5 (or MLogP is over 4.15);

4. There are more than 10 H-bond acceptors (expressed as the sum of Ns and Os).

Compound classes that are substrates for biological transporters are exceptions to the rule.

The rule of 5 has been extensively used in the pharmaceutical industry as a way to screen out candidates at the early stage of drug discovery. However, it is well known that compounds which violate these rules can still be very successful as drugs.