Lipinski Rule of Five Calculator
Check whether a molecule is likely to be orally active. Enter a SMILES and the calculator evaluates Lipinski's rule of five plus the Veber extension for polar surface area and flexibility.
Multiple molecules are allowed — one per line.
What is Lipinski's rule of five?
Christopher Lipinski observed in 1997 that most orally administered drugs satisfy four simple physicochemical limits. A compound that violates more than one of them is statistically less likely to reach the market. The "five" comes from the fact that every threshold is a multiple of five.
| Rule | Limit | Why it matters |
|---|---|---|
| Molecular weight | ≤ 500 Da | Large molecules permeate membranes poorly |
| logP (lipophilicity) | ≤ 5 | Too lipophilic means poor aqueous solubility |
| Hydrogen bond donors | ≤ 5 | Each donor costs energy to desolvate |
| Hydrogen bond acceptors | ≤ 10 | Same, for acceptors |
Veber rules
Veber et al. (2002) added two more predictors of oral bioavailability, which this calculator also reports:
- TPSA ≤ 140 Ų — polar surface area above this usually means poor absorption
- Rotatable bonds ≤ 10 — more flexibility means more conformational entropy cost
Frequently asked questions
Does passing the rules guarantee a drug?
No. The rules are a cheap filter, not a prediction of efficacy or safety. Many approved drugs violate one rule, and many rule-compliant compounds fail in trials.
Are these rules applied to natural products?
Not reliably. Natural products and PROTACs routinely violate the rule of five yet are still biologically active — the rules were derived from synthetic oral drug libraries.
Where do the numbers come from?
All descriptors are calculated by OpenBabel from the structure alone — no external database or lookup table is involved.