chembl-database — База данных биоактивных молекул и мишеней

--- name: chembl-database description: Query ChEMBL bioactive molecules and drug discovery data. Search compounds by structure/properties, retrieve bioactivity data (IC50, Ki), find inhibitors, perform SAR studies, for medicinal chemistry. license: Unknown metadata: skill-author: K-Dense Inc. --- # ChEMBL Database ## Overview ChEMBL is a manually curated database of bioactive molecules maintained by the European Bioinformatics Institute (EBI), containing over 2 million compounds, 19 million bioactivity measurements, 13,000+ drug targets, and data on approved drugs and clinical candidates. Access and query this data programmatically using the ChEMBL Python client for drug discovery and medicinal chemistry research. ## When to Use This Skill This skill should be used when: - **Compound searches**: Finding molecules by name, structure, or properties - **Target information**: Retrieving data about proteins, enzymes, or biological targets - **Bioactivity data**: Querying IC50, Ki, EC50, or other activity measurements - **Drug information**: Looking up approved drugs, mechanisms, or indications - **Structure searches**: Performing similarity or substructure searches - **Cheminformatics**: Analyzing molecular properties and drug-likeness - **Target-ligand relationships**: Exploring compound-target interactions - **Drug discovery**: Identifying inhibitors, agonists, or bioactive molecules ## Installation and Setup ### Python Client The ChEMBL Python client is required for programmatic access: ```bash uv pip install chembl_webresource_client ``` ### Basic Usage Pattern ```python from chembl_webresource_client.new_client import new_client # Access different endpoints molecule = new_client.molecule target = new_client.target activity = new_client.activity drug = new_client.drug ``` ## Core Capabilities ### 1. Molecule Queries **Retrieve by ChEMBL ID:** ```python molecule = new_client.molecule aspirin = molecule.get('CHEMBL25') ``` **Search by name:** ```python results = molecule.filter(pref_name__icontains='aspirin') ``` **Filter by properties:** ```python # Find small molecules (MW <= 500) with favorable LogP results = molecule.filter( molecule_properties__mw_freebase__lte=500, molecule_properties__alogp__lte=5 ) ``` ### 2. Target Queries **Retrieve target information:** ```python target = new_client.target egfr = target.get('CHEMBL203') ``` **Search for specific target types:** ```python # Find all kinase targets kinases = target.filter( target_type='SINGLE PROTEIN', pref_name__icontains='kinase' ) ``` ### 3. Bioactivity Data **Query activities for a target:** ```python activity = new_client.activity # Find potent EGFR inhibitors results = activity.filter( target_chembl_id='CHEMBL203', standard_type='IC50', standard_value__lte=100, standard_units='nM' ) ``` **Get all activities for a compound:** ```python compound_activities = activity.filter( molecule_chembl_id='CHEMBL25', pchembl_value__isnull=False ) ``` ### 4. Structure-Based Searches **Similarity search:** ```python similarity = new_client.similarity # Find compounds similar to aspirin similar = similarity.filter( smiles='CC(=O)Oc1ccccc1C(=O)O', similarity=85 # 85% similarity threshold ) ``` **Substructure search:** ```python substructure = new_client.substructure # Find compounds containing benzene ring results = substructure.filter(smiles='c1ccccc1') ``` ### 5. Drug Information **Retrieve drug data:** ```python drug = new_client.drug drug_info = drug.get('CHEMBL25') ``` **Get mechanisms of action:** ```python mechanism = new_client.mechanism mechanisms = mechanism.filter(molecule_chembl_id='CHEMBL25') ``` **Query drug indications:** ```python drug_indication = new_client.drug_indication indications = drug_indication.filter(molecule_chembl_id='CHEMBL25') ``` ## Query Workflow ### Workflow 1: Finding Inhibitors for a Target 1. **Identify the target** by searching by name: ```python targets = new_client.target.filter(pref_name__icontains='EGFR') target_id = targets[0]['target_chembl_id'] ``` 2. **Query bioactivity data** for that target: ```python activities = new_client.activity.filter( target_chembl_id=target_id, standard_type='IC50', standard_value__lte=100 ) ``` 3. **Extract compound IDs** and retrieve details: ```python compound_ids = [act['molecule_chembl_id'] for act in activities] compounds = [new_client.molecule.get(cid) for cid in compound_ids] ``` ### Workflow 2: Analyzing a Known Drug 1. **Get drug information**: ```python drug_info = new_client.drug.get('CHEMBL1234') ``` 2. **Retrieve mechanisms**: ```python mechanisms = new_client.mechanism.filter(molecule_chembl_id='CHEMBL1234') ``` 3. **Find all bioactivities**: ```python activities = new_client.activity.filter(molecule_chembl_id='CHEMBL1234') ``` ### Workflow 3: Structure-Activity Relationship (SAR) Study 1. **Find similar compounds**: ```python similar = new_client.similarity.filter(smiles='query_smiles', similarity=80) ``` 2. **Get activities for each compound**: ```python for compound in similar: activities = new_client.activity.filter( molecule_chembl_id=compound['molecule_chembl_id'] ) ``` 3. **Analyze property-activity relationships** using molecular properties from results. ## Filter Operators ChEMBL supports Django-style query filters: - `__exact` - Exact match - `__iexact` - Case-insensitive exact match - `__contains` / `__icontains` - Substring matching - `__startswith` / `__endswith` - Prefix/suffix matching - `__gt`, `__gte`, `__lt`, `__lte` - Numeric comparisons - `__range` - Value in range - `__in` - Value in list - `__isnull` - Null/not null check ## Data Export and Analysis Convert results to pandas DataFrame for analysis: ```python import pandas as pd activities = new_client.activity.filter(target_chembl_id='CHEMBL203') df = pd.DataFrame(list(activities)) # Analyze results print(df['standard_value'].describe()) print(df.groupby('standard_type').size()) ``` ## Performance Optimization ### Caching The client automatically caches results for 24 hours. Configure caching: ```python from chembl_webresource_client.settings import Settings # Disable caching Settings.Instance().CACHING = False # Adjust cache expiration (seconds) Settings.Instance().CACHE_EXPIRE = 86400 ``` ### Lazy Evaluation Queries execute only when data is accessed. Convert to list to force execution: ```python # Query is not executed yet results = molecule.filter(pref_name__icontains='aspirin') # Force execution results_list = list(results) ``` ### Pagination Results are paginated automatically. Iterate through all results: ```python for activity in new_client.activity.filter(target_chembl_id='CHEMBL203'): # Process each activity print(activity['molecule_chembl_id']) ``` ## Common Use Cases ### Find Kinase Inhibitors ```python # Identify kinase targets kinases = new_client.target.filter( target_type='SINGLE PROTEIN', pref_name__icontains='kinase' ) # Get potent inhibitors for kinase in kinases[:5]: # First 5 kinases activities = new_client.activity.filter( target_chembl_id=kinase['target_chembl_id'], standard_type='IC50', standard_value__lte=50 ) ``` ### Explore Drug Repurposing ```python # Get approved drugs drugs = new_client.drug.filter() # For each drug, find all targets for drug in drugs[:10]: mechanisms = new_client.mechanism.filter( molecule_chembl_id=drug['molecule_chembl_id'] ) ``` ### Virtual Screening ```python # Find compounds with desired properties candidates = new_client.molecule.filter( molecule_properties__mw_freebase__range=[300, 500], molecule_properties__alogp__lte=5, molecule_properties__hba__lte=10, molecule_properties__hbd__lte=5 ) ``` ## Resources ### scripts/example_queries.py Ready-to-use Python functions demonstrating common ChEMBL query patterns: - `get_molecule_info()` - Retrieve molecule details by ID - `search_molecules_by_name()` - Name-based molecule search - `find_molecules_by_properties()` - Property-based filtering - `get_bioactivity_data()` - Query bioactivities for targets - `find_similar_compounds()` - Similarity searching - `substructure_search()` - Substructure matching - `get_drug_info()` - Retrieve drug information - `find_kinase_inhibitors()` - Specialized kinase inhibitor search - `export_to_dataframe()` - Convert results to pandas DataFrame Consult this script for implementation details and usage examples. ### references/api_reference.md Comprehensive API documentation including: - Complete endpoint listing (molecule, target, activity, assay, drug, etc.) - All filter operators and query patterns - Molecular properties and bioactivity fields - Advanced query examples - Configuration and performance tuning - Error handling and rate limiting Refer to this document when detailed API information is needed or when troubleshooting queries. ## Important Notes ### Data Reliability - ChEMBL data is manually curated but may contain inconsistencies - Always check `data_validity_comment` field in activity records - Be aware of `potential_duplicate` flags ### Units and Standards - Bioactivity values use standard units (nM, uM, etc.) - `pchembl_value` provides normalized activity (-log scale) - Check `standard_type` to understand measurement type (IC50, Ki, EC50, etc.) ### Rate Limiting - Respect ChEMBL's fair usage policies - Use caching to minimize repeated requests - Consider bulk downloads for large datasets - Avoid hammering the API with rapid consecutive requests ### Chemical Structure Formats - SMILES strings are the primary structure format - InChI keys available for compounds - SVG images can be generated via the image endpoint ## Additional Resources - ChEMBL website: https://www.ebi.ac.uk/chembl/ - API documentation: https://www.ebi.ac.uk/chembl/api/data/docs - Python client GitHub: https://github.com/chembl/chembl_webresource_client - Interface documentation: https://chembl.gitbook.io/chembl-interface-documentation/ - Example notebooks: https://github.com/chembl/notebooks