Pharmaclaw Tox Agent

Toxicology Agent for pharma drug safety profiling from SMILES. Computes RDKit ADMET descriptors (logP, TPSA, MW, HBD, HBA, rotatable bonds), Lipinski Rule of Five violations, Veber rule checks, QED drug-likeness score, and PAINS substructure alerts. Outputs risk classification (Low/Medium/High) with full property report. Chains from Chemistry Query (receives SMILES) and feeds into IP Expansion for safer derivative suggestions. Triggers on tox, toxicology, safety, ADMET, hepatotox, carcinogen, risk, PAINS, drug safety, Lipinski, Veber, QED.

PharmaClaw Toxicology Agent

Overview

Predictive toxicology and drug safety profiling agent for the PharmaClaw pipeline. Screens drug candidates via RDKit descriptors, rule-based filters (Lipinski Ro5, Veber), QED scoring, and PAINS alerts to flag safety risks early in the discovery process.

Quick Start

bash

# Analyze a compound
python scripts/tox_agent.py "CC(=O)Nc1ccc(O)cc1"

# Default (ethanol)
python scripts/tox_agent.py

Capabilities

Check	Method	Threshold
Lipinski Ro5	MW, LogP, HBD, HBA	MW>500, LogP>5, HBD>5, HBA>10
Veber Rules	TPSA, Rotatable Bonds	TPSA>140, RotB>10
QED Score	RDKit QED module	0-1 (higher = more drug-like)
PAINS Alerts	Substructure matching	Known assay interference patterns
Ring Analysis	Aromatic/total ring count	Complexity indicator

Decision Tree

• SMILES input → RDKit descriptor calculation → Rule-based screening
• Lipinski violations = 0 AND PAINS = 0 → Risk: Low
• Any violations or PAINS hits → Risk: Medium/High
• High risk flagged → Recommend analogs via Chemistry Query / IP Expansion

Output Format

json

{
  "lipinski_viol": 0,
  "veber_viol": 0,
  "qed": 0.737,
  "pains": 0,
  "risk": "Low",
  "props": {
    "mw": 151.2,
    "logp": 1.02,
    "tpsa": 49.3,
    "hbd": 2,
    "hba": 2,
    "rotb": 1,
    "rings": 1,
    "arom": 1
  }
}

Risk Classification

• Low: No Lipinski violations, no PAINS alerts, QED > 0.5
• Medium: 1-2 Lipinski violations OR low QED
• High: 3+ Lipinski violations, PAINS hits, or multiple Veber violations

Chain Integration

• Receives from: Chemistry Query (SMILES), Pharmacology (ADME flags)
• Feeds into: IP Expansion (safer derivative suggestions), Synthesis (avoid toxic intermediates)
• Cross-references: Market Intel (FAERS adverse events for similar structures)

Dependencies

• rdkit-pypi — Molecular descriptors, QED, substructure matching

Scripts

• scripts/tox_agent.py — Main agent: ToxAgent class with analyze(smiles) method

Limitations

• PAINS screening uses simplified substructure set (production should use full PAINS catalog)
• No Ames mutagenicity or hERG channel prediction (descriptor-based proxies planned)
• LD50 estimation not yet implemented (QSAR model planned for future version)