By name: ADME-assessment description: Based on a compound, get its ADME and other properties. Assess compounds for ADME (Absorption, Distribution, Metabolism, Excretion) characteristics, chemical properties, and drug-likeness using PubChem. Use when the user wants to evaluate compound suitability as a lead candidate. Triggers include requests like "assess drug-likeness for [compound]", "evaluate ADME for [CID]", "ADME assessment", "check Lipinski rules for [compound]", "molecular properties of [drug]", or "is [compound] a good lead candidate". Accepts PubChem CIDs, compound names, SMILES, or InChI as input.
ADME Assessment Skill
Assess compounds for lead optimization by evaluating chemical properties, drug-likeness, and ADME characteristics via PubChem MCP tools.
Workflow Overview
- Resolve compound identifier → Get PubChem CID from name/SMILES/InChI
- Get molecular properties → MW, logP, TPSA, HBD, HBA, rotatable bonds
- Assess drug-likeness → Lipinski Rule of Five, Veber rules, PAINS filters
- Predict ADME properties → Absorption, distribution, metabolism, excretion
- Analyze molecular complexity → Synthetic accessibility, structural features
- Format output → Present assessment as markdown table with pass/fail indicators
Step 1: Resolve Compound Identifier
Convert user input to PubChem CID using appropriate PubChem MCP tool:
By name or identifier:
PubChem:search_compounds(query="<compound_name>")
By SMILES:
PubChem:search_by_smiles(smiles="<SMILES_string>")
By InChI:
PubChem:search_by_inchi(inchi="<InChI_string>")
By CAS number:
PubChem:search_by_cas_number(cas_number="<CAS>")
If multiple CIDs are provided (batch assessment), process each compound sequentially.
Step 2: Get Molecular Properties
PubChem:get_compound_properties(cid=<CID>)
Extract key properties:
- Molecular Weight (MW)
- LogP (partition coefficient)
- TPSA (topological polar surface area)
- HBD (hydrogen bond donors)
- HBA (hydrogen bond acceptors)
- Rotatable Bonds
- Ring Count
- Aromatic Ring Count
Also retrieve structural information:
PubChem:get_compound_info(cid=<CID>)
Returns: molecular formula, SMILES, InChI, canonical structure.
Step 3: Assess Drug-Likeness
PubChem:assess_drug_likeness(cid=<CID>)
Evaluates against established rules:
Lipinski Rule of Five
| Rule | Threshold | Interpretation |
|---|---|---|
| MW | ≤ 500 Da | Good oral absorption |
| LogP | ≤ 5 | Adequate lipophilicity |
| HBD | ≤ 5 | Hydrogen bond donors |
| HBA | ≤ 10 | Hydrogen bond acceptors |
One violation allowed for oral drugs
Veber Rules (Oral Bioavailability)
| Rule | Threshold |
|---|---|
| TPSA | ≤ 140 Ų |
| Rotatable Bonds | ≤ 10 |
PAINS Filters
Identifies pan-assay interference compounds (false positives in HTS).
Step 4: Predict ADME Properties
PubChem:predict_admet_properties(cid=<CID>)
Extract ADME-relevant predictions (exclude toxicity):
Absorption
- Intestinal absorption
- Caco-2 permeability
- P-glycoprotein substrate/inhibitor
Distribution
- Blood-brain barrier penetration
- Plasma protein binding
- Volume of distribution
Metabolism
- CYP450 substrate (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4)
- CYP450 inhibitor predictions
Excretion
- Renal clearance predictions
- Half-life estimates (if available)
Step 5: Analyze Molecular Complexity
PubChem:analyze_molecular_complexity(cid=<CID>)
Assess:
- Synthetic accessibility score (1-10, lower = easier)
- Fraction sp3 carbons (higher = more 3D character)
- Stereocenters count
- Structural complexity metrics
Optional - for pharmacophore insights:
PubChem:get_pharmacophore_features(cid=<CID>)
Step 6: Format Output
Present results in this format:
## ADME Assessment for [COMPOUND_NAME]
**Compound**: [NAME] (CID: [CID])
**Formula**: [FORMULA]
**SMILES**: [SMILES]
### Molecular Properties
| Property | Value | Threshold | Status |
|----------|-------|-----------|--------|
| Molecular Weight | X Da | ≤ 500 | ✓/✗ |
| LogP | X | ≤ 5 | ✓/✗ |
| TPSA | X Ų | ≤ 140 | ✓/✗ |
| HBD | X | ≤ 5 | ✓/✗ |
| HBA | X | ≤ 10 | ✓/✗ |
| Rotatable Bonds | X | ≤ 10 | ✓/✗ |
### Drug-Likeness Summary
| Rule Set | Violations | Status |
|----------|------------|--------|
| Lipinski Ro5 | X/4 | Pass/Fail |
| Veber | X/2 | Pass/Fail |
| PAINS | X alerts | Pass/Concern |
### ADME Predictions
| Property | Prediction | Confidence |
|----------|------------|------------|
| Intestinal Absorption | High/Low | X% |
| BBB Penetration | Yes/No | X% |
| CYP3A4 Substrate | Yes/No | X% |
| CYP2D6 Inhibitor | Yes/No | X% |
| ... | ... | ... |
### Complexity Analysis
| Metric | Value | Interpretation |
|--------|-------|----------------|
| Synthetic Accessibility | X/10 | Easy/Moderate/Difficult |
| Fsp3 | X | Low/Moderate/High 3D character |
| Stereocenters | X | Complexity consideration |
### Overall Assessment
[Brief summary: Is this a good lead candidate? Key strengths and liabilities.]
Error Handling
- Compound not found: If search returns no results, suggest alternative names, check SMILES validity, or ask for CID directly
- Missing ADME predictions: Note which predictions are unavailable; some compounds lack sufficient data
- Multiple matches: If search returns multiple CIDs, list top matches and ask user to specify
Example Usage
User: "Assess erlotinib as a lead compound"
Claude workflow:
PubChem:search_compounds(query="erlotinib")→ CID 176870PubChem:get_compound_properties(cid=176870)PubChem:assess_drug_likeness(cid=176870)PubChem:predict_admet_properties(cid=176870)(exclude toxicity)PubChem:analyze_molecular_complexity(cid=176870)- Format and present assessment table
Batch Assessment
For multiple compounds, present a comparison table:
## ADME Comparison
| Compound | MW | LogP | TPSA | Ro5 | Veber | PAINS | Synth. Access. |
|----------|-----|------|------|-----|-------|-------|----------------|
| Compound A | X | X | X | ✓ | ✓ | ✓ | 3.2 |
| Compound B | X | X | X | ✓ | ✗ | ✓ | 5.1 |