lifesciences-pharmacology

name

lifesciences-pharmacology

description

Queries pharmacology databases (ChEMBL, PubChem, IUPHAR, Open Targets) via MCP tools for drug mechanisms, target identification, bioactivity profiling, and indication discovery. Falls back to curl when MCP is unavailable. This skill should be used when the user asks to "find drug mechanisms", "identify drug targets", "analyze bioactivity data", "discover drug indications", or mentions ChEMBL IDs, mechanisms of action, IC50/Ki values, drug-target relationships, or compound similarity searches.

Pharmacology API Skills

Query pharmacology databases via MCP tools (primary) or curl (fallback).

Grounding Rule

All drug names, mechanisms, targets, and bioactivity values MUST come from API results. Do NOT provide drug information from training knowledge. If a query returns no results, report "No results found."

MCP Token Budgeting (slim Parameter)

All MCP tools in this skill support a slim parameter for token-efficient queries:

When to use slim=true:

• LOCATE phase: Fast candidate lists (returns ~20 tokens/entity vs ~115-300 tokens)
• Batch operations: Resolving multiple entities in a single turn
• Exploration: Quick overviews without full metadata

When to use slim=false (default):

• RETRIEVE phase: Need full metadata with cross-references
• Validation: Verifying detailed properties
• Graph persistence: Collecting complete entity records

Example:

# 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

Task	Pattern	MCP Tool (primary)	Curl Endpoint (fallback)
Search compounds	LOCATE	chembl_search_compounds	ChEMBL /molecule/search
Get compound	RETRIEVE	chembl_get_compound	ChEMBL /molecule/{id}
Drug mechanism	RETRIEVE	(curl only)	ChEMBL /mechanism
Drug indications	RETRIEVE	(curl only)	ChEMBL /drug_indication
Bioactivity data	RETRIEVE	(curl only)	ChEMBL /activity
Find drugs for target	LOCATE	opentargets_get_target	Open Targets GraphQL knownDrugs
Compound by name	LOCATE	pubchem_search_compounds	PubChem /compound/name/{name}
Ligand interactions	RETRIEVE	iuphar_get_ligand	IUPHAR /ligands/{id}/interactions

ID Format Reference

Database	API Argument (bare)	Graph CURIE	Example
ChEMBL compound	CHEMBL3137309	CHEMBL:3137309	Bare for API (no colon)
ChEMBL target	CHEMBL4860	CHEMBL:4860	Same pattern
PubChem	2244 (CID)	PubChem:2244	Bare numeric for API

API Reliability & Fallback Patterns

Primary	Fallback	When to Switch
ChEMBL chembl_get_compound (detail)	Open Targets opentargets_get_target	On HTTP 500 (common for detail endpoints)
ChEMBL chembl_search_compounds (search)	(generally reliable — uses Elasticsearch)	Retry once, then report failure
ChEMBL /mechanism	Open Targets mechanismOfAction field	On HTTP 500

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

API	Limit	Auth Required	Production Throttle
ChEMBL	~2 req/s	No	0.5s delay in production
PubChem	5 req/s	No	—
IUPHAR	10 req/s	No	—

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