ChEMBL Database Query

Prerequisites

1. uv: Read the uv skill and follow its Setup instructions to ensure uv is installed and on PATH.
2. User Notification: If .licenses/chembl_database_LICENSE.txt does not already exist in the workspace root directory then (1) prominently notify the user to check the terms at https://chembl.gitbook.io/chembl-interface-documentation/about, then (2) create the file recording the notification text and timestamp.

Core Rules

• [!IMPORTANT] Use the Utility Scripts: You MUST ALWAYS use the provided utility script scripts/chembl_api.py for all ChEMBL API interactions, including checking status. NEVER use curl or custom Python requests to query the ChEMBL API directly. This ensures rate limit is enfoced and also retries on network errors.

• Output to File (Required): The --output flag is required for every subcommand. All JSON results are written to the specified file. After running the command, read the output file with jq or your own code to extract the data. List results are typically wrapped in a JSON array keyed by the endpoint name (e.g., molecules, activities).

• Notification: If this skill is used, ensure this is mentioned in the output.

Utility Script

All ChEMBL API queries use one script with subcommands:

uv run scripts/chembl_api.py <subcommand> --output <file> [options]

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1. Check API Status

uv run scripts/chembl_api.py status --output /tmp/status.json

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2. Molecule Queries

Fetch by ChEMBL ID: bash uv run scripts/chembl_api.py molecule --id CHEMBL25 --output /tmp/mol.json

Search by name: bash uv run scripts/chembl_api.py molecule --search "aspirin" --limit 3 --output /tmp/mol_search.json

Batch fetch: bash uv run scripts/chembl_api.py molecule --ids "CHEMBL25;CHEMBL1642" --limit 10 --output /tmp/mol_batch.json

Filter by properties: bash uv run scripts/chembl_api.py molecule --filter molecule_properties__mw_freebase__lte=500 --limit 5 --output /tmp/mol_filter.json

Filter by range: bash uv run scripts/chembl_api.py molecule --filter molecule_properties__mw_freebase__range=150,200 --limit 5 --output /tmp/mol_range.json

Download SDF structure file: bash uv run scripts/chembl_api.py molecule --id CHEMBL25 --dl_format sdf --output /tmp/aspirin.sdf

Tip: SDF/MOL files can be passed directly to tools like PyMOL or RDKit for 3D visualization and analysis.

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3. Target Queries

Search for targets: bash uv run scripts/chembl_api.py target --search "EGFR" --limit 5 --output /tmp/targets.json

Fetch by ID: bash uv run scripts/chembl_api.py target --id CHEMBL203 --output /tmp/egfr.json

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4. Bioactivity Data

Fetch activity by ID: bash uv run scripts/chembl_api.py activity --id 31863 --output /tmp/act.json

Search activities: bash uv run scripts/chembl_api.py activity --search "EGFR" --limit 5 --output /tmp/act_search.json

Filter activities for a target: bash uv run scripts/chembl_api.py activity --filter target_chembl_id=CHEMBL203 standard_type=IC50 --limit 10 --output /tmp/egfr_ic50.json

Normalize bioactivity units to nM: bash uv run scripts/chembl_api.py activity --filter target_chembl_id=CHEMBL203 standard_type=IC50 --limit 5 --normalize --output /tmp/egfr_normalized.json

Important: Bioactivity values come in various units (nM, µM, pM). Use --normalize to convert all values to nM for consistent comparison. Each record will include normalized_value_nM and normalization_note.

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5. Drug Information

Fetch drug details: bash uv run scripts/chembl_api.py drug --id CHEMBL25 --output /tmp/drug.json

Drug indications: bash uv run scripts/chembl_api.py drug_indication --filter molecule_chembl_id=CHEMBL25 --limit 10 --output /tmp/indications.json

Filter indications by phase: bash uv run scripts/chembl_api.py drug_indication --filter molecule_chembl_id=CHEMBL25 max_phase_for_ind=4.0 --limit 10 --output /tmp/approved_indications.json

Drug warnings: bash uv run scripts/chembl_api.py drug_warning --limit 5 --output /tmp/warnings.json

Mechanisms of action: bash uv run scripts/chembl_api.py mechanism --filter molecule_chembl_id=CHEMBL25 --limit 5 --output /tmp/mech.json

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6. Structure-Based Searches

Note: Both similarity and substructure searches are performed server-side on ChEMBL's pre-indexed database. They do not require a local RDKit installation.

Similarity search (SMILES + threshold): bash uv run scripts/chembl_api.py similarity --smiles "CC(=O)Oc1ccccc1C(=O)O" --similarity 85 --limit 5 --output /tmp/similar.json

Substructure search (SMILES): bash uv run scripts/chembl_api.py substructure --smiles "c1ccccc1" --limit 5 --output /tmp/substruct.json

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7. Compound Image

Download a 2D structure image (SVG by default, scalable for publication):

uv run scripts/chembl_api.py image --id CHEMBL25 --output /tmp/chembl25.svg

Options:

• --dimensions: Image size in pixels (max 500, default 500).
• --engine: Rendering engine (default: rdkit).
• --img_format: Output format — svg (default, vector) or png (raster).

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8. Cross-Referencing with Other Databases

ChEMBL integrates with UniProt, Ensembl, PubChem, and other databases. Common cross-referencing patterns:

Find a ChEMBL target from a UniProt accession: bash uv run scripts/chembl_api.py target --filter target_components__accession=P00533 --limit 5 --output /tmp/uniprot_target.json

Resolve any ChEMBL ID to its entity type: bash uv run scripts/chembl_api.py chembl_id_lookup --id CHEMBL203 --output /tmp/lookup.json

Look up cross-reference sources: bash uv run scripts/chembl_api.py xref_source --limit 10 --output /tmp/xrefs.json

Tip: Use the target_component endpoint to find UniProt accessions, gene names, and protein sequences for any ChEMBL target.

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9. Pagination

All list endpoints support --limit and --offset for pagination:

# First page: 2 results starting at offset 0
uv run scripts/chembl_api.py molecule --limit 2 --offset 0 --output /tmp/page1.json

# Second page: next 2 results starting at offset 2
uv run scripts/chembl_api.py molecule --limit 2 --offset 2 --output /tmp/page2.json

The response includes page_meta with total_count, limit, offset, next, and previous links. Use successive --offset values to page through large result sets.

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10. Other Endpoints

All remaining endpoints follow the same pattern:

uv run scripts/chembl_api.py <subcommand> --output <file> [--id ID | --ids ID1;ID2 | --search QUERY] [--limit N] [--offset N] [--filter KEY=VAL ...]

Key subcommands at a glance:

• molecule (searchable: true): Molecules/compounds — the primary entry point
• target (searchable: true): Drug targets (proteins, organisms, etc.)
• activity (searchable: true): Bioactivity data (IC50, Ki, EC50, etc.)
• drug (searchable: false): Approved drugs
• mechanism (searchable: false): Mechanisms of action
• assay (searchable: true): Assay descriptions
• similarity (searchable: false): Similarity search (special)
• substructure (searchable: false): Substructure search (special)
• image (searchable: false): Compound image download (special)

Full subcommand list:

• activity_supp (searchable: false): Supplementary activity data
• assay_class (searchable: false): Assay classifications
• atc_class (searchable: false): ATC drug classifications
• binding_site (searchable: false): Binding site information
• biotherapeutic (searchable: false): Biotherapeutic molecules
• cell_line (searchable: false): Cell line details
• chembl_id_lookup (searchable: true): ChEMBL ID resolution
• chembl_release (searchable: false): Database release info
• compound_record (searchable: false): Compound records
• compound_structural_alert (searchable: false): Structural alerts
• document (searchable: true): Literature documents
• document_similarity (searchable: false): Document similarity
• drug_indication (searchable: false): Drug indications
• drug_warning (searchable: false): Drug safety warnings
• go_slim (searchable: false): GO slim terms
• metabolism (searchable: false): Metabolism data
• molecule_form (searchable: false): Molecule forms (salts/parents)
• organism (searchable: false): Organisms
• protein_classification (searchable: true): Protein classifications
• source (searchable: false): Data sources
• target_component (searchable: false): Target protein components
• target_relation (searchable: false): Target relationships
• tissue (searchable: false): Tissue types
• xref_source (searchable: false): Cross-reference sources
• status (searchable: false): API status check (special)

Common Options

• --output FILE: Required. Output file path for JSON results.
• --id ID: Fetch a single record by ID.
• --ids ID1;ID2;...: Batch fetch multiple records.
• --search QUERY: Free-text search (only for searchable endpoints, marked ✓).
• --limit N: Max results to return (default: 5).
• --offset N: Pagination offset.
• --filter KEY=VAL: Filter parameters (can specify multiple).
• --normalize: (activity only) Normalize values to nM.
• --dl_format sdf|mol: (molecule only) Download structure file.

Reference

• API Endpoints Reference: See references/api_endpoints.md for the full list of endpoints and filter operators.

Workflow

1. Use status --output /tmp/status.json to verify the API is available.
2. Search for targets, molecules, or drugs using the relevant subcommand.
3. Read the output JSON file to extract IDs and data.
4. Use IDs from search results to fetch detailed records.
5. Query activity with filters to get bioactivity data for targets/molecules. Use --normalize when comparing values across studies.
6. Use similarity or substructure for server-side structure-based queries.
7. Download compound images with image or structure files with molecule --dl_format sdf.
8. Use target --filter target_components__accession=<UniProt> to cross- reference with UniProt.