My Easy Science
Lipinski Rule of Five Checker
Four simple rules that predict whether a molecule is likely to be absorbed when swallowed. Check any drug in seconds.
Inputs
Worked example
Loads a hand-worked test case from the spec (manual entry, so it works offline).
The molecule
Try a real drug
Each rule against its limit
| Rule | Limit | This molecule | Result |
|---|---|---|---|
| Tap Check to see the numbers. | |||
Lipinski violations
— violations
Number of Lipinski rules broken. Zero or one is usually fine; two or more is a warning sign for oral absorption.
Checked against five hand-worked examples (see the page source comments).
Results are shown to 2 decimal places, except TPSA, which is shown to 1 decimal place.
Enter the four values, then tap Check the four rules.
| Rule | Value | Limit | Result |
|---|---|---|---|
| Molecular weight | — | ≤ 500 | — |
| LogP | — | ≤ 5 | — |
| H-bond donors | — | ≤ 5 | — |
| H-bond acceptors | — | ≤ 10 | — |
| Rotatable bonds (Veber) | — | ≤ 10 | — |
| TPSA (Veber) | — | ≤ 140 Ų | — |
Why this rule exists
Oral drugs have to dissolve in the gut, cross a fatty membrane, and then dissolve in blood. A very heavy molecule crosses slowly, a very greasy one (high logP) does not dissolve well, and too many hydrogen-bond donors or acceptors make the molecule cling to water instead of slipping through the membrane. The four limits are the rough edges of that trade-off, found by looking at the oral drugs that had actually made it to the clinic.
A guide, not a law. Many natural products, antibiotics and transporter substrates break these rules and still work.
For learning only. Not for patient care decisions. Always check with a qualified professional and the product label.
How it works
In 1997 Christopher Lipinski looked at the oral drugs that had made it to the clinic and found that almost all of them shared four features: a molecular weight under 500, a LogP under 5, no more than 5 hydrogen bond donors, and no more than 10 hydrogen bond acceptors. The numbers are all multiples of five, which is why it is called the Rule of Five. A molecule that breaks one rule is usually still fine. A molecule that breaks two or more is much less likely to be absorbed well when swallowed, so it is a warning sign, not a verdict.
Aspirin passes all four: weight 180, LogP 1.2, 1 donor, 4 acceptors. Atorvastatin breaks two: its weight is 559 and its LogP is 5.7, yet it is a successful oral drug, which shows the rules are a guide, not a law. Cyclosporine breaks two as well, weight 1203 and 12 acceptors, and it still works by mouth, but only because it is a natural product that the gut handles in a special way. Veber added two more useful rules in 2002: 10 or fewer rotatable bonds, and a polar surface area of 140 Ų or less, both of which also track with good oral absorption.
LogP deserves a note. It is the log of how a molecule splits between octanol and water, so a high LogP means greasy and poorly soluble, and a low LogP means water-loving and poorly able to cross a membrane. Different programs give slightly different LogP values for the same molecule, so use the same source when you compare drugs, and check the source when a value sits near a limit.