Pharmacology API Skills

# LOCATE: Find top 10 gene candidates (slim=true for speed)
Call `hgnc_search_genes` with: {"query": "TNF", "slim": true, "page_size": 10}
→ Returns minimal fields: ID, symbol, name only (~20 tokens each)

# RETRIEVE: Get full record for validation (slim=false, default)
Call `hgnc_get_gene` with: {"hgnc_id": "HGNC:11892"}
→ Returns complete metadata with cross-references (~115 tokens)

Impact: Using slim=true during LOCATE enables 5-10x more entities per LLM turn without context overflow.

Reference: This token budgeting pattern is detailed in reference/prior-art-api-patterns.md (Section 7.1).

LOCATE → RETRIEVE Patterns

ChEMBL: Compound Search & Details

LOCATE: Search compound by name

PRIMARY (MCP tool):

Call `chembl_search_compounds` with: {"query": "venetoclax"}
→ Returns: ChEMBL IDs, preferred names, max phase

FALLBACK (curl):

curl -s "https://www.ebi.ac.uk/chembl/api/data/molecule/search?q=venetoclax&format=json" \
  | jq '.molecules[:1][] | {chembl_id: .molecule_chembl_id, name: .pref_name, max_phase: .max_phase}'

RETRIEVE: Get compound by ChEMBL ID

PRIMARY (MCP tool):

Call `chembl_get_compound` with: {"chembl_id": "CHEMBL3137309"}
→ May return 500 error (common for detail endpoints) — fall back to Open Targets

FALLBACK (curl):

curl -s "https://www.ebi.ac.uk/chembl/api/data/molecule/CHEMBL3137309?format=json" \
  | jq '{id: .molecule_chembl_id, name: .pref_name, formula: .molecule_properties.full_molformula, mw: .molecule_properties.full_mwt}'

Open Targets: Drug Discovery (PRIMARY — More Reliable Than ChEMBL)

LOCATE: Find drugs targeting a protein

PRIMARY (MCP tool):

Call `opentargets_get_target` with: {"ensembl_id": "ENSG00000171791"}
→ Returns: knownDrugs with drug name, mechanismOfAction, phase in one call

FALLBACK (curl):

curl -s -X POST "https://api.platform.opentargets.org/api/v4/graphql" \
  -H "Content-Type: application/json" \
  -d '{"query": "{ target(ensemblId: \"ENSG00000171791\") { knownDrugs(size: 25) { rows { drug { name id } mechanismOfAction phase } } } }"}'

Open Targets knownDrugs Pagination:

• Use size parameter only (e.g., size: 25) — this is the reliable pattern
• Do NOT use page or index — these cause intermittent failures
• For paginated results, use cursor (returned in the response) as the continuation token
• If first query fails, retry with size only (no other pagination params)

Note: Requires Ensembl Gene ID (ENSG...). Get this from HGNC cross-references or Ensembl lookup.

ChEMBL: Drug Mechanisms (Critical for Graph Edges) — curl only

RETRIEVE: Get mechanism for drug (Drug → Target edge)

curl -s "https://www.ebi.ac.uk/chembl/api/data/mechanism?molecule_chembl_id=CHEMBL3137309&format=json" \
  | jq '.mechanisms[] | {action: .action_type, mechanism: .mechanism_of_action, target_id: .target_chembl_id}'

RETRIEVE: Find all drugs for target (Target → Drugs edge)

curl -s "https://www.ebi.ac.uk/chembl/api/data/mechanism?target_chembl_id=CHEMBL4860&format=json" \
  | jq '.mechanisms[] | {drug_id: .molecule_chembl_id, action: .action_type, mechanism: .mechanism_of_action}'

ChEMBL: Drug Indications — curl only

RETRIEVE: Get indications for drug (Drug → Disease edge)

curl -s "https://www.ebi.ac.uk/chembl/api/data/drug_indication?molecule_chembl_id=CHEMBL3137309&format=json" \
  | jq '.drug_indications[:5][] | {disease: .mesh_heading, efo: .efo_term, phase: .max_phase_for_ind}'

ChEMBL: Bioactivity Data (Potency Metrics) — curl only

RETRIEVE: Get activity data (IC50, Ki, EC50)

curl -s "https://www.ebi.ac.uk/chembl/api/data/activity?molecule_chembl_id=CHEMBL3137309&format=json&limit=10" \
  | jq '.activities[] | {target: .target_pref_name, type: .standard_type, value: .standard_value, units: .standard_units}'

PubChem: Compound Data

LOCATE: Get compound by name

PRIMARY (MCP tool):

Call `pubchem_search_compounds` with: {"query": "aspirin"}
→ Returns: CID, molecular formula, properties

FALLBACK (curl):

curl -s "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/name/aspirin/JSON" \
  | jq '.PC_Compounds[0] | {cid: .id.id.cid}'

RETRIEVE: Get properties by CID

PRIMARY (MCP tool):

Call `pubchem_get_compound` with: {"cid": "2244"}
→ Returns: molecular formula, weight, IUPAC name

FALLBACK (curl):

curl -s "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/2244/property/MolecularFormula,MolecularWeight,IUPACName/JSON" \
  | jq '.PropertyTable.Properties[0]'

IUPHAR/GtoPdb: Pharmacology

LOCATE: Search ligands

PRIMARY (MCP tool):

Call `iuphar_search_ligands` with: {"query": "ibuprofen"}
→ Returns: ligand ID, name, type, approved status

FALLBACK (curl):

curl -s "https://www.guidetopharmacology.org/services/ligands?name=ibuprofen" \
  | jq '.[:1][] | {id: .ligandId, name, type, approved}'

RETRIEVE: Get ligand-target interactions

PRIMARY (MCP tool):

Call `iuphar_get_ligand` with: {"ligand_id": "2713"}
→ Returns: target interactions, action types, affinities

FALLBACK (curl):

curl -s "https://www.guidetopharmacology.org/services/ligands/2713/interactions" \
  | jq '.[:3][] | {target: .targetName, action: .action, affinity}'

Drug Repurposing Workflow (LOCATE → RETRIEVE Chain)

# Step 1: LOCATE — Find target for known drug (curl — mechanism endpoint)
TARGET=$(curl -s "https://www.ebi.ac.uk/chembl/api/data/mechanism?molecule_chembl_id=CHEMBL3137309&format=json" \
  | jq -r '.mechanisms[0].target_chembl_id')

# Step 2: RETRIEVE — Find other drugs for same target
curl -s "https://www.ebi.ac.uk/chembl/api/data/mechanism?target_chembl_id=$TARGET&format=json" \
  | jq '.mechanisms[] | {drug: .molecule_chembl_id, mechanism: .mechanism_of_action}'

# Step 3: RETRIEVE — Get indications for alternative drug
curl -s "https://www.ebi.ac.uk/chembl/api/data/drug_indication?molecule_chembl_id=CHEMBL2107358&format=json" \
  | jq '.drug_indications[:3][] | {disease: .mesh_heading, phase: .max_phase_for_ind}'

Quick Reference

ID Format Reference

API Reliability & Fallback Patterns

Critical: ChEMBL detail endpoints (/molecule/{id}) frequently return 500 errors (EBI server issues). ChEMBL search endpoints (/molecule/search?q=...) are generally reliable because they use Elasticsearch. When detail fails, use Open Targets as primary drug discovery source.

Rate Limits

Query Best Practices

Drug Discovery vs Repurposing

• Drug repurposing: Use max_phase >= 2 filter (want clinical validation, shorter approval path)
• General discovery: No phase filter (include preclinical tools, mechanism probes, research reagents)
• Target validation: No phase filter needed for mechanism studies

Gain-of-Function Disease Filter

For diseases caused by protein overactivation (e.g., FOP from constitutive ACVR1):

• INCLUDE: inhibitors, antagonists, negative modulators
• EXCLUDE: agonists, positive modulators, activators
• Check mechanismOfAction field from Open Targets or action_type from ChEMBL

Query Efficiency

• Check mechanisms (/mechanism endpoint) before bioactivity data
• Use target_chembl_id for reverse lookups (find drugs for target)
• Limit activity queries with &limit=10 for exploration

See Also

• lifesciences-graph-builder: Orchestrator for full Fuzzy-to-Fact protocol
• lifesciences-clinical: Open Targets, ClinicalTrials.gov clinical endpoints