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Safety Filter Scoring

Safety filter scoring evaluates molecules against structural alert databases to identify potentially problematic compounds. This is a scored summary of the detailed Structural Alerts screening.

What It Measures​

Safety filter scoring tests molecules against multiple catalogs:

CatalogPatternsFocus
PAINS A/B/C~480Pan-assay interference compounds — frequent hitters in HTS
Brenk~105Unfavorable chemical moieties for drug development
NIH~180NIH MLSMR screening exclusion filters
ZINC~95Drug-likeness and reactivity filters
ChEMBL~700+Combined from 7 pharma sub-catalogs (see below)

ChEMBL Sub-Catalogs​

The ChEMBL structural alerts combine filters from 7 pharmaceutical industry sources:

Sub-CatalogSourceFocus
BMSBristol-Myers SquibbReactive functional groups and chemical liabilities
DundeeUniversity of DundeePromiscuous compound filters for screening
GlaxoGlaxoSmithKlineUndesirable moieties and toxicophores
InpharmaticaInpharmatica Ltd.Chemical liabilities and ADMET flags
LINTLead Identification NoiseNoise-causing patterns in lead identification
MLSMRNIH/MLSMRMolecular Libraries Screening Center Network filters
SureChEMBLEMBL-EBIPatent literature structural alerts

Each sub-catalog targets different aspects of compound quality. When ChEMBL alerts are enabled, all 7 sub-catalogs are screened simultaneously.

All pattern matching uses RDKit's FilterCatalog module with SMARTS substructure matching.

Scoring Output​

The safety filter score provides a pass/fail summary:

{
"safety_filters": {
"pains": {
"passed": true,
"alerts": [],
"alert_count": 0
},
"brenk": {
"passed": true,
"alerts": [],
"alert_count": 0
},
"nih": {
"passed": true,
"alerts": [],
"alert_count": 0
},
"zinc": {
"passed": true,
"alerts": [],
"alert_count": 0
},
"chembl": {
"passed": true,
"total_alerts": 0
},
"all_passed": true,
"total_alerts": 0,
"interpretation": "No safety alerts detected"
}
}

Interpretation​

ResultInterpretationRecommendation
All passedNo alerts foundGood safety profile for screening
PAINS onlyAssay interference riskReview assay compatibility before screening
Multiple catalogsMultiple issuesInvestigate further, consider excluding

Safety Filter vs. Structural Alerts​

Safety Filter Scoring (this page):

  • Part of comprehensive scoring API
  • Pass/fail summary only
  • Quick screening
  • Included in batch processing

Structural Alerts:

  • Detailed alert information
  • Matched atoms identified
  • Pattern names and descriptions
  • Dedicated API endpoint

Use safety filter scoring for quick filtering, then use detailed structural alerts for investigation.

Use in Batch Processing​

In batch mode, safety filter pass rate is reported:

{
"statistics": {
"safety_pass_rate": 0.91
}
}

This indicates 91% of molecules pass all safety filters.

Best Practices​

  1. Use for prioritization: Not absolute rejection criteria
  2. Review alerts: Always investigate specific alerts for hits
  3. Consider context: 87 FDA-approved drugs match PAINS patterns
  4. Check assay type: PAINS alerts are assay-specific
  5. Document decisions: Record why you accepted/rejected flagged molecules

Next Steps​