Understanding the Results

Interpreting SwissADME Results 

The output is divided into several sections. SwissADME will process each molecule and present the results in a clear, organized table. Let us focus on the most important parts for a beginner.

A. Chemical Structure & Bioavailability Radar 

2D Structure: Confirms the molecule analyzed.

Bioavailability Radar: A hexagonal plot assessing six key drug-likeness parameters:

1. Lipophilicity (XLOGP3)

2. Size (Molecular Weight)

3. Polarity (Topological Polar Surface Area, TPSA)

4. Solubility (Log S)

5. Saturation (Fraction of sp³ carbons)

6. Flexibility (Number of rotatable bonds)

Figure 1: Chemical Structure & Bioavailability Radar and Physicochemical Properties 

B. Physicochemical Properties 

1. Molecular Weight (MW): Should ideally be <500 Da (Lipinski’s Rule of Five).

2. Topological Polar Surface Area (TPSA): Predicts membrane permeability (optimal: <140 Ų).

3. Number of Rotatable Bonds: Affects flexibility (optimal: ≤10).

4. H-bond Donors/Acceptors: Should be ≤5 and ≤10, respectively.

C. Lipophilicity (LogP)

Lipophilicity is the partition coefficient between n-octanol and water (log Po/w ) 

• Consensus LogP: Average of five prediction methods (XLOGP3, WLOGP, MLOGP, SILICOS-IT, iLOGP) (Figure 2).

• Optimal range: -0.7 to +5.0 for good oral bioavailability

D. Water Solubility (LogS)

• Predicts solubility in water (ESOL, Ali, and SILICOS-IT models)-higher values indicate better solubility.

E. Pharmacokinetics 

Evaluate individual ADME behaviours of the molecule under investigation.

• Gastrointestinal (GI) Absorption: High/Low prediction. 

• Blood-Brain Barrier (BBB) Permeability: Yes/No. 

• CYP450 Metabolism: Identifies potential interactions with liver enzymes. 

• P-glycoprotein Substrate: Predicts efflux pump interactions.

F. Druglikeness

Druglikeness assesses qualitatively the chance for a molecule to become an oral drug with good bioavailability.

Druglikeness Rules: Lipinski, Ghose, Veber, Egan, and Muegge (Figure 5)

Lipinski's Rule of Five (RO5). This is one of the most famous rules of thumb for evaluating druglikeness. It predicts if a compound is likely to have good oral absorption. A molecule generally follows the rule if it meets the following criteria:

Molecular Weight (MW): ≤500 g/mol

LogP (lipophilicity): ≤5

H-bond Donors: ≤5

H-bond Acceptors: ≤10

Applying the Results

• If Lipinski’s Rule of Five is violated → The molecule may have poor oral bioavailability.

• If solubility is too low → Reformulation or chemical modification might be necessary.

REFERENCES

Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1). https://doi.org/10.1038/srep42717.

Lipinski, C. A. (2004). Lead- and drug-like compounds: the rule-of-five revolution. Drug Discovery Today Technologies, 1(4), 337–341. https://doi.org/10.1016/j.ddtec.2004.11.007.

SwissADME official website: http://www.swissadme.ch