Free PhysChem Calculator
Draw a molecule or paste SMILES to instantly calculate MW, LogP, TPSA, Fsp3, ESOL solubility, QED score, Lipinski Ro5 and Veber criteria. Structural alerts are highlighted directly on the molecule structure. No signup required.
What is Lipinski's Rule of Five?
In 1997, Lipinski and colleagues at Pfizer analysed compounds that had reached Phase II clinical trials and identified property ranges correlated with good oral absorption. The Rule of Five flags poor absorption when:
Molecular weight
LogP
Lipophilicity
Hydrogen-bond donors
NH and OH groups
Hydrogen-bond acceptors
N and O atoms
It is called the "Rule of Five" because every threshold is a multiple of five: a useful reminder that these are round-number heuristics, not precise cutoffs. Compounds violating two or more parameters are statistically less likely to succeed as oral drugs, but these are guidelines for probability, not laws of nature.
Veber's Criteria: flexibility and polarity
In 2002, Veber and colleagues at GlaxoSmithKline analysed over 1,100 drug candidates tested for oral bioavailability in rats. They found that molecular flexibility and polarity were strong predictors of oral absorption, independent of molecular weight:
≤ 140
Topological polar surface area
TPSA, Ų
≤ 10
Rotatable bonds
≤ 12
Total hydrogen-bond count
HBD + HBA
TPSA measures the surface area contributed by polar atoms (nitrogen, oxygen, and their attached hydrogens). Higher polarity reduces passive membrane permeability. Rotatable bonds measure molecular flexibility: a more flexible molecule must pay a larger conformational entropy cost to adopt the geometry needed for membrane permeation, which correlates with reduced oral bioavailability. The total H-bond count captures overall polarity in a complementary way to TPSA.
This calculator checks all three Veber criteria alongside Lipinski's Rule of Five and displays all seven properties in a radar chart for easy visual comparison.
What is QED?
QED (Quantitative Estimate of Drug-likeness) was introduced by Bickerton et al. in Nature Chemistry (2012). Instead of applying binary pass/fail thresholds, QED maps each of eight molecular properties through a desirability function derived from the distributions observed in approved oral drugs, then combines them into a single score between 0 and 1.
The eight QED properties
MW
Molecular weight
LogP
Lipophilicity
HBD
H-bond donors
HBA
H-bond acceptors
PSA
Polar surface area
RotB
Rotatable bonds
Arom
Aromatic rings
Alerts
Structural alerts
Structural alerts check against 116 SMARTS patterns flagging reactive or toxic substructures. Matched atoms are colour-coded and highlighted directly on the molecule structure so you can see exactly which part of the molecule triggered each alert.
QED Score Interpretation
Because QED uses weighted desirability functions rather than hard cutoffs, it captures a more nuanced picture of drug-likeness than any single rule set.
Guidelines, not rules: the "beyond Ro5" space
The Ro5 predicts the likelihood of adequate absorption, not overall clinical success. Many approved drugs violate one or more thresholds:
Atorvastatin (MW 559 Da) exceeds the MW threshold yet is one of the most commercially successful drugs in history.
Erythromycin (MW 734 Da, ~30% bioavailability), rifampicin (MW 823 Da, ~90% bioavailability), and cyclosporine A (MW 1203 Da, 20-60% bioavailability) have been successful oral medicines for decades.
More recently, HCV protease inhibitors like glecaprevir (MW 838 Da) and cancer drugs like venetoclax (MW 868 Da) achieve effective oral exposure.
of oral drugs approved since 2000 exceed 500 Da. Of the four Lipinski parameters, LogP > 5 is arguably the most consequential violation. High lipophilicity correlates with increased attrition across all stages of development.
Curious about the science behind these drugs?
Explore how atorvastatin, venetoclax, and over 50 other famous molecules were discovered, optimised, and brought to patients. Real science, real stories.